11-62707136-G-T

Variant names:

• chr11-62707136-G-T
• rs115116507
• NM_001122955.4:c.60C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001122955.4(BSCL2):​c.60C>A​(p.Asp20Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D20H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: BSCL2 NM_001122955.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 8 publications found

Genes affected

BSCL2 (HGNC:15832): (BSCL2 lipid droplet biogenesis associated, seipin) 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]

HNRNPUL2-BSCL2 (HGNC:49189): (HNRNPUL2-BSCL2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2) and BSCL2 (Berardinelli-Seip congenital lipodystrophy 2 (seipin)) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

GNG3 (HGNC:4405): (G protein subunit gamma 3) Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The gamma subunit determines the specificity of which signaling pathways will be affected by this particular complex. The protein encoded by this gene represents the gamma subunit of both inhibitory and stimulatory complexes. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06799096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122955.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSCL2	NM_001122955.4	MANE Select	c.60C>A	p.Asp20Glu	missense	Exon 1 of 11	NP_001116427.1
	BSCL2	NM_001386027.1		c.60C>A	p.Asp20Glu	missense	Exon 2 of 12	NP_001372956.1
	BSCL2	NM_001386028.1		c.60C>A	p.Asp20Glu	missense	Exon 2 of 12	NP_001372957.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSCL2	ENST00000360796.10	TSL:1 MANE Select	c.60C>A	p.Asp20Glu	missense	Exon 1 of 11	ENSP00000354032.5
	BSCL2	ENST00000405837.5	TSL:1	c.60C>A	p.Asp20Glu	missense	Exon 2 of 12	ENSP00000385332.1
	HNRNPUL2-BSCL2	ENST00000403734.2	TSL:2	n.*111C>A		non_coding_transcript_exon	Exon 14 of 24	ENSP00000456010.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151944 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151944 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74212

African (AFR) AF: 0.0000242 AC: 1 AN: 41300

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	4.9
DANN	Benign	0.87
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.65	T
PhyloP100		-0.73
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.24
Sift	Uncertain	0.024	D
Sift4G	Benign	0.15	T
Vest4		0.042
MutPred		0.12		Loss of loop (P = 0.0986)
MVP		0.45
ClinPred		0.030	T
GERP RS		-4.2
PromoterAI		-0.010	Neutral
gMVP		0.026
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs115116507; hg19: chr11-62474608;