Mutagenetix > Incidental Mutation

Incidental Mutation 'R7867:Tpm3'

607821

Institutional Source

Beutler Lab

Gene Symbol

Tpm3

Ensembl Gene

ENSMUSG00000027940

Gene Name

tropomyosin 3, gamma

Synonyms

hTM30nm, Tpm-5, skalphaTM.2, Trop-5, gamma-TM, hTMnm, Tm5NM, Tpm5

MMRRC Submission

045919-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7867 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

89979958-90008209 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 89993775 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Serine at position 89 (L89S)

Ref Sequence

ENSEMBL: ENSMUSP00000113978 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029549] [ENSMUST00000118566] [ENSMUST00000119158] [ENSMUST00000119570] [ENSMUST00000121503] [ENSMUST00000127955] [ENSMUST00000149432]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000029549
AA Change: L52S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000029549
Gene: ENSMUSG00000027940
AA Change: L52S

Domain	Start	End	E-Value	Type
Pfam:Tropomyosin_1	4	117	3.9e-22	PFAM
Pfam:Tropomyosin	12	248	7.2e-93	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000118566
AA Change: L52S

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000113056
Gene: ENSMUSG00000027940
AA Change: L52S

Domain	Start	End	E-Value	Type
Pfam:Tropomyosin_1	3	117	2e-21	PFAM
Pfam:Tropomyosin	12	248	1.7e-100	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000119158
AA Change: L52S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000113219
Gene: ENSMUSG00000027940
AA Change: L52S

Domain	Start	End	E-Value	Type
Pfam:Tropomyosin_1	4	117	1.7e-22	PFAM
Pfam:Tropomyosin	12	247	3.9e-96	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000119570
AA Change: L89S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000113978
Gene: ENSMUSG00000027940
AA Change: L89S

Domain	Start	End	E-Value	Type
Pfam:Tropomyosin_1	8	154	4.2e-35	PFAM
Pfam:CLZ	10	75	1.2e-9	PFAM
Pfam:Tropomyosin	49	285	3.7e-91	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000121503
AA Change: L88S

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000113578
Gene: ENSMUSG00000027940
AA Change: L88S

Domain	Start	End	E-Value	Type
Pfam:Tropomyosin_1	7	153	1.3e-36	PFAM
Pfam:Tropomyosin	48	284	4.7e-103	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000127955

Predicted Effect

probably benign
Transcript: ENSMUST00000149432

SMART Domains

Protein: ENSMUSP00000114229
Gene: ENSMUSG00000027940

Domain	Start	End	E-Value	Type
Pfam:Tropomyosin	1	70	1.6e-28	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the tropomyosin family of actin-binding proteins. Tropomyosins are dimers of coiled-coil proteins that provide stability to actin filaments and regulate access of other actin-binding proteins. Mutations in this gene result in autosomal dominant nemaline myopathy and other muscle disorders. This locus is involved in translocations with other loci, including anaplastic lymphoma receptor tyrosine kinase (ALK) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), which result in the formation of fusion proteins that act as oncogenes. There are numerous pseudogenes for this gene on different chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
PHENOTYPE: Homozygous inactivation of this gene results in early embryonic death, prior to blastocyst formation. Mice homozygous for a targeted allele lacking exon 9 exhibit dysmorphic T-tubules and contraction in skeletal muscles. [provided by MGI curators]

Allele List at MGI

All alleles(76) : Targeted(5) Gene trapped(71)

Other mutations in this stock

Total: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca13	T	A	11: 9,212,139 (GRCm39)		probably null	Het
Abcf1	C	A	17: 36,272,890 (GRCm39)	K252N	probably damaging	Het
Abi3	C	T	11: 95,724,851 (GRCm39)	A211T	possibly damaging	Het
Acaca	A	T	11: 84,140,350 (GRCm39)	D608V	possibly damaging	Het
Akap10	A	G	11: 61,791,272 (GRCm39)	Y396H	probably damaging	Het
Ap3b1	C	G	13: 94,619,771 (GRCm39)	S778W	unknown	Het
Arb2a	T	C	13: 78,050,837 (GRCm39)	M165T	probably benign	Het
Baat	G	A	4: 49,502,925 (GRCm39)	L66F	probably benign	Het
Cachd1	A	G	4: 100,845,759 (GRCm39)	N981S	probably damaging	Het
Cacna1c	C	T	6: 118,753,407 (GRCm39)	R243H		Het
Cdh23	T	A	10: 60,150,390 (GRCm39)	I2527F	probably damaging	Het
Cinp	A	G	12: 110,840,557 (GRCm39)	V198A	probably benign	Het
Clec4d	T	C	6: 123,244,123 (GRCm39)		probably null	Het
Cnn3	A	G	3: 121,248,704 (GRCm39)	I204V	probably benign	Het
Cpxm2	C	A	7: 131,650,800 (GRCm39)	G620V	probably damaging	Het
Ctrl	A	C	8: 106,659,497 (GRCm39)	S93A	probably benign	Het
Cyp2d34	A	G	15: 82,501,425 (GRCm39)	V301A	possibly damaging	Het
Dnaaf5	G	T	5: 139,147,565 (GRCm39)	K376N	probably damaging	Het
Eno2	C	T	6: 124,740,137 (GRCm39)	D300N	probably damaging	Het
Entrep3	T	A	3: 89,093,083 (GRCm39)	Y280*	probably null	Het
Fam117b	T	A	1: 60,014,046 (GRCm39)	N440K	probably damaging	Het
Fam131a	A	G	16: 20,514,584 (GRCm39)	S62G	probably benign	Het
Fancm	T	A	12: 65,163,240 (GRCm39)		probably null	Het
Fancm	A	G	12: 65,165,173 (GRCm39)	D1506G	probably benign	Het
Fhad1	C	A	4: 141,632,902 (GRCm39)	V1201L	probably benign	Het
Gdpd4	T	A	7: 97,623,185 (GRCm39)	C265*	probably null	Het
Gm3127	A	T	14: 15,425,888 (GRCm39)	T98S	probably null	Het
Gpsm1	A	T	2: 26,230,448 (GRCm39)	D466V	probably benign	Het
Gramd1a	T	G	7: 30,842,992 (GRCm39)	K76Q	probably damaging	Het
Gstp3	T	C	19: 4,108,808 (GRCm39)	D24G	probably damaging	Het
Kalrn	G	A	16: 33,810,161 (GRCm39)	T2531I	possibly damaging	Het
Klk7	C	A	7: 43,462,333 (GRCm39)	D108E	probably damaging	Het
Klkb1	A	G	8: 45,740,002 (GRCm39)	S97P	probably damaging	Het
Krt13	T	C	11: 100,012,008 (GRCm39)	D105G	probably damaging	Het
Lingo2	T	A	4: 35,709,302 (GRCm39)	H226L	probably benign	Het
Lrba	T	C	3: 86,275,896 (GRCm39)	S1755P	probably damaging	Het
Marf1	A	G	16: 13,946,470 (GRCm39)	V1217A	probably damaging	Het
Mtss1	A	T	15: 58,842,858 (GRCm39)	V118E	possibly damaging	Het
Mug1	T	A	6: 121,850,593 (GRCm39)	D696E	probably benign	Het
Ndufa3	C	T	7: 3,623,003 (GRCm39)	P56L	probably damaging	Het
Nop56	T	A	2: 130,120,205 (GRCm39)	C471S	possibly damaging	Het
Obscn	T	A	11: 58,891,652 (GRCm39)	H6960L	unknown	Het
Or13a22	C	T	7: 140,073,049 (GRCm39)	T166I	probably benign	Het
Pcdhb10	A	C	18: 37,546,619 (GRCm39)	Q565P	probably benign	Het
Pde6g	T	A	11: 120,338,953 (GRCm39)	H79L	possibly damaging	Het
Phrf1	G	T	7: 140,836,524 (GRCm39)	M265I	unknown	Het
Pkd2	T	C	5: 104,630,986 (GRCm39)	F470S	probably damaging	Het
Plekhm1	T	A	11: 103,271,153 (GRCm39)	D446V	probably damaging	Het
Prkaca	A	T	8: 84,721,963 (GRCm39)	T325S	probably benign	Het
Proz	A	T	8: 13,111,027 (GRCm39)		probably benign	Het
Pten	T	C	19: 32,792,894 (GRCm39)	F238L	probably benign	Het
Ptpn21	G	A	12: 98,671,435 (GRCm39)	L198F	probably damaging	Het
Rbm5	A	T	9: 107,628,930 (GRCm39)	S394T	probably benign	Het
Scaf8	T	G	17: 3,227,994 (GRCm39)	S408A	unknown	Het
Slc41a3	T	A	6: 90,617,909 (GRCm39)	F312I	probably damaging	Het
Soat2	T	A	15: 102,059,598 (GRCm39)		probably null	Het
Sorcs1	C	A	19: 50,218,698 (GRCm39)	G595*	probably null	Het
Spopfm1	G	C	3: 94,173,154 (GRCm39)	S50T	probably benign	Het
Stox1	G	T	10: 62,500,723 (GRCm39)	D612E	probably benign	Het
Suco	T	C	1: 161,665,365 (GRCm39)	I530M	possibly damaging	Het
Syne2	A	G	12: 76,030,501 (GRCm39)		probably null	Het
Thbd	G	A	2: 148,249,664 (GRCm39)	A68V	probably damaging	Het
Tmem109	A	T	19: 10,855,466 (GRCm39)	M4K	unknown	Het
Tmub1	G	C	5: 24,651,664 (GRCm39)	P85R	possibly damaging	Het
Tnk2	A	C	16: 32,500,053 (GRCm39)	Q1039H	probably damaging	Het
Unc13b	C	T	4: 43,232,573 (GRCm39)	R432*	probably null	Het
Vmn2r59	T	A	7: 41,661,707 (GRCm39)	I703F	probably damaging	Het
Xylt1	T	A	7: 117,074,749 (GRCm39)	I122N	probably benign	Het
Zc3h12c	T	C	9: 52,055,248 (GRCm39)	E187G	probably damaging	Het

Other mutations in Tpm3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00481:Tpm3	APN	3	89,995,024 (GRCm39)	missense	probably damaging	0.99
IGL00949:Tpm3	APN	3	89,997,165 (GRCm39)	missense	probably damaging	1.00
IGL01955:Tpm3	APN	3	89,995,742 (GRCm39)	missense	probably benign	0.00
IGL01970:Tpm3	APN	3	89,997,135 (GRCm39)	missense	probably damaging	1.00
IGL02605:Tpm3	APN	3	89,995,753 (GRCm39)	missense	probably benign	0.13
IGL03352:Tpm3	APN	3	89,995,052 (GRCm39)	critical splice donor site	probably null
IGL03375:Tpm3	APN	3	89,981,079 (GRCm39)	missense	possibly damaging	0.83
P0045:Tpm3	UTSW	3	89,998,400 (GRCm39)	critical splice donor site	probably null
R0006:Tpm3	UTSW	3	89,994,968 (GRCm39)	splice site	probably benign
R0006:Tpm3	UTSW	3	89,994,968 (GRCm39)	splice site	probably benign
R0024:Tpm3	UTSW	3	89,994,756 (GRCm39)	splice site	probably null
R0086:Tpm3	UTSW	3	89,997,399 (GRCm39)	unclassified	probably benign
R1487:Tpm3	UTSW	3	89,997,389 (GRCm39)	splice site	probably null
R5235:Tpm3	UTSW	3	89,993,802 (GRCm39)	missense	probably damaging	1.00
R6639:Tpm3	UTSW	3	89,987,109 (GRCm39)	missense	probably damaging	0.99
R7089:Tpm3	UTSW	3	89,980,029 (GRCm39)	start gained	probably benign
R7212:Tpm3	UTSW	3	89,998,361 (GRCm39)	missense	probably benign
R8322:Tpm3	UTSW	3	89,981,011 (GRCm39)	intron	probably benign
R8701:Tpm3	UTSW	3	89,994,987 (GRCm39)	missense	possibly damaging	0.68
R9167:Tpm3	UTSW	3	89,994,824 (GRCm39)	missense	probably benign	0.13
X0020:Tpm3	UTSW	3	89,994,881 (GRCm39)	critical splice donor site	probably null

Predicted Primers

PCR Primer
(F):5'- ACCAATGGGAGTTCTTAGCTAGG -3'
(R):5'- GTCAGAGCCACTATCAGCTTTAC -3'

Sequencing Primer
(F):5'- TTCTTAGCTAGGGAAGGAGGAAACTG -3'
(R):5'- TCTGCAGTGCCAGGGATG -3'

Posted On

2019-12-20