11-62690468-G-C

Position:

• chr11-62690468-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122955.4(BSCL2):​c.1288C>G​(p.Pro430Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P430S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BSCL2 NM_001122955.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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]

BSCL2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08261928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSCL2	NM_001122955.4	c.1288C>G	p.Pro430Ala	missense_variant	11/11	ENST00000360796.10	NP_001116427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSCL2	ENST00000360796.10	c.1288C>G	p.Pro430Ala	missense_variant	11/11	1	NM_001122955.4	ENSP00000354032.5
HNRNPUL2-BSCL2	ENST00000403734.2	n.*1339C>G		non_coding_transcript_exon_variant	24/24	2		ENSP00000456010.1
HNRNPUL2-BSCL2	ENST00000403734.2	n.*1339C>G		3_prime_UTR_variant	24/24	2		ENSP00000456010.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.8
DANN	Benign	0.70
DEOGEN2	Benign	0.15	.;.;.;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.62	T;T;T;.;.;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.083	T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.8	.;.;.;L;L;L
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.4	D;N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.039	D;D;D;T;T;T
Sift4G	Benign	0.36	T;T;T;T;T;T
Polyphen		0.043	.;.;.;B;B;B
Vest4		0.22, 0.22, 0.23, 0.23
MutPred		0.16		.;.;.;Loss of loop (P = 9e-04);Loss of loop (P = 9e-04);Loss of loop (P = 9e-04);
MVP		0.54
ClinPred		0.092	T
GERP RS		-7.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.019
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs377310581; hg19: chr11-62457940;