rs943542

chr10-95432567-A-Cchr10-95432567-A-Gchr10-95432567-A-T

Variant summary

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

The NM_001034954.3(SORBS1):c.182T>G(p.Leu61Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. L61P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SORBS1 NM_001034954.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66

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]

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=0.23275876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.182T>G	p.Leu61Arg	missense_variant	6/33	ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.182T>G	p.Leu61Arg	missense_variant	6/33	5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Benign	-0.16
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;.;.;D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;N;N;N;.;N;N;N;.;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.46	N;N;N;N;N;.;N;N;N;N;N;N;.
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D;D;D;D;.;D;D;D;D;D;D;.
Sift4G	Benign	0.072	T;T;D;D;T;T;T;D;D;D;D;D;.
Polyphen		0.13	B;B;B;P;B;.;B;P;B;B;.;B;.
Vest4		0.28
MutPred		0.63		Gain of MoRF binding (P = 0.0184);.;Gain of MoRF binding (P = 0.0184);Gain of MoRF binding (P = 0.0184);Gain of MoRF binding (P = 0.0184);.;Gain of MoRF binding (P = 0.0184);Gain of MoRF binding (P = 0.0184);Gain of MoRF binding (P = 0.0184);.;Gain of MoRF binding (P = 0.0184);.;.;
MVP		0.47
MPC		0.32
ClinPred		0.58	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.19

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: rs943542; hg19: chr10-97192324;