Mutagenetix > Incidental Mutation

Incidental Mutation 'R7401:Bscl2'

574208

Institutional Source

Beutler Lab

Gene Symbol

Bscl2

Ensembl Gene

ENSMUSG00000071657

Gene Name

Berardinelli-Seip congenital lipodystrophy 2 (seipin)

Synonyms

seipin, Gng3lg

MMRRC Submission

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7401 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

8837467-8848683 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 8846550 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 280 (F280L)

Ref Sequence

ENSEMBL: ENSMUSP00000127685 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000086058] [ENSMUST00000096257] [ENSMUST00000159634] [ENSMUST00000159653] [ENSMUST00000160556] [ENSMUST00000160897] [ENSMUST00000171649]

AlphaFold

Q9Z2E9

Predicted Effect

possibly damaging
Transcript: ENSMUST00000086058
AA Change: F220L

PolyPhen 2 Score 0.934 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000083224
Gene: ENSMUSG00000071657
AA Change: F220L

Domain	Start	End	E-Value	Type
Pfam:Seipin	37	243	3.9e-71	PFAM
Blast:PAC	269	306	4e-7	BLAST
low complexity region	353	371	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000096257

SMART Domains

Protein: ENSMUSP00000093976
Gene: ENSMUSG00000071656

Domain	Start	End	E-Value	Type
signal peptide	1	19	N/A	INTRINSIC
FN3	83	162	2.81e-5	SMART
transmembrane domain	194	216	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000159634
AA Change: F220L

PolyPhen 2 Score 0.934 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000125422
Gene: ENSMUSG00000071657
AA Change: F220L

Domain	Start	End	E-Value	Type
Pfam:Seipin	37	243	3.9e-71	PFAM
Blast:PAC	269	306	4e-7	BLAST
low complexity region	353	371	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000159653
AA Change: F74L

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

SMART Domains

Protein: ENSMUSP00000123920
Gene: ENSMUSG00000071657
AA Change: F74L

Domain	Start	End	E-Value	Type
Pfam:Seipin	1	97	1.2e-33	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000160556
AA Change: F220L

PolyPhen 2 Score 0.934 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000123976
Gene: ENSMUSG00000071657
AA Change: F220L

Domain	Start	End	E-Value	Type
Pfam:Seipin	37	243	3.9e-71	PFAM
Blast:PAC	269	306	4e-7	BLAST
low complexity region	353	371	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000160897

SMART Domains

Protein: ENSMUSP00000125250
Gene: ENSMUSG00000071657

Domain	Start	End	E-Value	Type
Pfam:Seipin	97	208	2.8e-34	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000171649
AA Change: F280L

PolyPhen 2 Score 0.567 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000127685
Gene: ENSMUSG00000071657
AA Change: F280L

Domain	Start	End	E-Value	Type
Pfam:Seipin	99	302	8.5e-66	PFAM
Blast:PAC	329	366	2e-6	BLAST
low complexity region	413	431	N/A	INTRINSIC

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the multi-pass transmembrane protein protein seipin. This protein localizes to the endoplasmic reticulum and may be important for lipid droplet morphology. Mutations in this gene have been associated with congenital generalized lipodystrophy type 2 or Berardinelli-Seip syndrome, a rare autosomal recessive disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Naturally occurring read-through transcription occurs between this locus and the neighboring locus HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2).[provided by RefSeq, Mar 2011]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit severe generalized lipodystrophy with hepatic steatosis, glucose intolerance, and insulin resistance. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2610318N02Rik	A	T	16: 17,118,404	L152Q	probably benign	Het
Abcg3	A	T	5: 104,966,774	N292K	probably damaging	Het
Adamts3	T	A	5: 89,707,450		probably null	Het
Adgrg7	T	C	16: 56,742,418	N519D	probably benign	Het
Adsl	A	G	15: 80,962,782	H263R	probably damaging	Het
Ak9	A	T	10: 41,423,004	D1567V	unknown	Het
Cacna1b	T	A	2: 24,679,294	T873S	probably benign	Het
Cacna1c	T	C	6: 119,052,708		probably null	Het
Cast	G	T	13: 74,808,458	A18E	unknown	Het
Ccdc114	A	C	7: 45,942,765	Q323P	probably damaging	Het
Cd207	A	C	6: 83,677,848		probably benign	Het
Cd79b	A	G	11: 106,312,852	S130P	probably benign	Het
Cfap52	A	T	11: 67,949,633	N157K	probably benign	Het
Cfap57	C	T	4: 118,614,931	V84I	probably benign	Het
Chaf1b	G	T	16: 93,884,380		probably benign	Het
Cntn1	A	G	15: 92,317,989	I968V	probably benign	Het
Cntn5	C	T	9: 9,833,461	V362I	probably benign	Het
Crem	A	G	18: 3,295,329	S80P	probably damaging	Het
Csnk1g3	C	T	18: 53,930,318	T267I	probably damaging	Het
Cyth1	A	T	11: 118,182,251	N274K	possibly damaging	Het
Dicer1	C	T	12: 104,712,278	G594S	probably benign	Het
Enpp1	C	T	10: 24,645,282	C849Y	probably damaging	Het
Fam193a	A	G	5: 34,465,635	E1189G	possibly damaging	Het
Fermt1	C	A	2: 132,917,559	V426L	probably benign	Het
Fes	A	G	7: 80,378,776		probably null	Het
Gm16486	T	C	8: 70,717,272	I1337T	probably benign	Het
Gmeb1	C	A	4: 132,225,774	L560F	probably damaging	Het
Hace1	T	C	10: 45,670,626	L452P	probably damaging	Het
Hecw2	T	A	1: 53,904,343	H975L	probably damaging	Het
Idh2	GGTCCCAG	GG	7: 80,098,329		probably benign	Het
Il1r2	T	A	1: 40,123,210	C338S	probably damaging	Het
Kcnb1	T	C	2: 167,188,284	S114G	probably damaging	Het
Lce1c	A	T	3: 92,680,316	T17S	unknown	Het
Lhfpl4	C	A	6: 113,176,666	L141F	possibly damaging	Het
Ms4a14	T	C	19: 11,302,230	E988G	possibly damaging	Het
Naip5	T	C	13: 100,219,696	Q1137R	probably benign	Het
Naip5	G	T	13: 100,219,697	Q1137K	not run	Het
Neurod1	T	A	2: 79,454,946	D31V	probably benign	Het
Neurod4	A	G	10: 130,271,058	C116R	probably damaging	Het
Nisch	A	G	14: 31,206,580	V28A	probably benign	Het
Olfr1174-ps	T	G	2: 88,311,428	M123L	probably benign	Het
Olfr1245	A	G	2: 89,575,105	V207A	probably benign	Het
Pabpc4l	A	T	3: 46,446,252	I319N	probably damaging	Het
Pabpc4l	T	A	3: 46,446,589	R207W	probably damaging	Het
Pcm1	G	A	8: 41,309,531	D1371N	probably damaging	Het
Peg10	G	GGTC	6: 4,756,452		probably benign	Het
Plxnc1	C	T	10: 94,871,005	A557T	probably benign	Het
Prkdc	T	A	16: 15,648,738	V58D	probably damaging	Het
Prpf40a	A	G	2: 53,156,947	V259A	probably benign	Het
Psmd3	A	T	11: 98,685,640	T123S	probably benign	Het
Ptgr2	G	T	12: 84,292,329		probably benign	Het
Ptprr	A	G	10: 116,048,236	H66R	probably benign	Het
Rftn2	A	G	1: 55,194,242		probably null	Het
Rsph14	T	A	10: 75,029,796	E70V	possibly damaging	Het
Slc24a5	G	A	2: 125,088,191	V471I	probably benign	Het
Sorbs1	G	C	19: 40,376,800	R180G	probably benign	Het
Spag9	A	T	11: 94,097,689	T862S	probably benign	Het
Ssbp2	T	A	13: 91,690,883	D291E	probably benign	Het
Supt5	T	C	7: 28,323,772	K329E	probably damaging	Het
Syne2	G	T	12: 75,967,381	K3115N	probably damaging	Het
Tars	A	T	15: 11,392,009	L239*	probably null	Het
Tbxa2r	T	C	10: 81,332,791	Y105H	probably benign	Het
Tesk1	T	A	4: 43,445,743	D265E	probably damaging	Het
Tril	T	C	6: 53,818,281	D652G	possibly damaging	Het
Tsga10	T	C	1: 37,834,187	R204G	probably null	Het
Twnk	A	G	19: 45,011,780	D645G	probably benign	Het
Umodl1	A	T	17: 30,998,148	D1118V	probably damaging	Het
Unc119	T	C	11: 78,347,245	I83T	probably benign	Het
Unc80	T	C	1: 66,646,415	W2233R	possibly damaging	Het
Vmn1r45	T	A	6: 89,933,434	T185S	possibly damaging	Het
Vmn2r111	G	T	17: 22,571,086	T313K	possibly damaging	Het
Wdr4	A	G	17: 31,509,832	L123S	probably damaging	Het
Zfpm2	A	G	15: 41,102,990	E957G	possibly damaging	Het

Other mutations in Bscl2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01908:Bscl2	APN	19	8845276	missense	probably damaging	0.99
IGL03206:Bscl2	APN	19	8843089	missense	probably damaging	0.97
R0193:Bscl2	UTSW	19	8847429	missense	probably benign	0.21
R1112:Bscl2	UTSW	19	8839734	missense	possibly damaging	0.90
R1513:Bscl2	UTSW	19	8841145	missense	probably damaging	1.00
R2049:Bscl2	UTSW	19	8845320	splice site	probably null
R2121:Bscl2	UTSW	19	8839782	nonsense	probably null
R2140:Bscl2	UTSW	19	8845320	splice site	probably null
R2142:Bscl2	UTSW	19	8845320	splice site	probably null
R2483:Bscl2	UTSW	19	8841150	missense	probably benign	0.01
R3623:Bscl2	UTSW	19	8841150	missense	probably benign	0.01
R4177:Bscl2	UTSW	19	8839756	missense	possibly damaging	0.85
R4675:Bscl2	UTSW	19	8848159	missense	possibly damaging	0.81
R4967:Bscl2	UTSW	19	8847980	missense	probably benign	0.02
R5051:Bscl2	UTSW	19	8845279	nonsense	probably null
R5446:Bscl2	UTSW	19	8846200	missense	possibly damaging	0.91
R6493:Bscl2	UTSW	19	8839774	missense	probably damaging	1.00
R6838:Bscl2	UTSW	19	8841381	missense	probably damaging	1.00
R7117:Bscl2	UTSW	19	8848514	missense	possibly damaging	0.68
R7923:Bscl2	UTSW	19	8847519	missense	probably benign	0.00
R8249:Bscl2	UTSW	19	8846520	missense	probably damaging	1.00
R8332:Bscl2	UTSW	19	8846230	missense	probably benign	0.23
R8748:Bscl2	UTSW	19	8847947	missense	probably damaging	0.99
R8870:Bscl2	UTSW	19	8847429	missense	probably benign	0.02
R8926:Bscl2	UTSW	19	8847984	critical splice donor site	probably null
R9249:Bscl2	UTSW	19	8843014	missense	probably damaging	1.00
R9691:Bscl2	UTSW	19	8839746	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- GAATTCGGTAAGTGGCTGACAG -3'
(R):5'- CTCTTGAAAGGTGACAAGCAC -3'

Sequencing Primer
(F):5'- CTGACAGAGTTAGGAGACAACTCTTC -3'
(R):5'- TGACAAGCACAGTGAAGCC -3'

Posted On

2019-09-13