10-95381766-G-T

Position:

• chr10-95381766-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001034954.3(SORBS1):​c.1572C>A​(p.Asp524Glu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SORBS1 NM_001034954.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21

Genes affected

SORBS1 (HGNC:14565): (sorbin and SH3 domain containing 1) This gene encodes a CBL-associated protein which functions in the signaling and stimulation of insulin. Mutations in this gene may be associated with human disorders of insulin resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

SORBS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.1572C>A	p.Asp524Glu	missense_variant	18/33	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.1572C>A	p.Asp524Glu	missense_variant	18/33	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	.;.;.;.;D;.;D;.;.;.;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D;D;.;.;D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.4	.;.;.;.;M;.;M;.;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	D;D;D;D;D;.;D;D;D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;D;D;D;D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.028	D;T;D;T;T;D;T;T;T;T;D;D
Polyphen		1.0	D;D;D;D;D;.;D;D;D;D;D;D
Vest4		0.72
MutPred		0.12		.;.;.;.;Gain of methylation at K521 (P = 0.0872);.;Gain of methylation at K521 (P = 0.0872);.;.;.;.;.;
MVP		0.66
MPC		0.72
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.46
gMVP		0.35

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: rs2274490; hg19: chr10-97141523;