dbSNP rs193920900: SORBS1:p.Arg1047Leu (chr10-95337020-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001034954.3(SORBS1):c.3140G>T(p.Arg1047Leu) 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. 15/22 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. R1047P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SORBS1
NM_001034954.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.420

Publications

3 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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=0.066365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3 link	c.3140G>T	p.Arg1047Leu	missense_variant	Exon 30 of 33	ENST00000371247.7	NP_001030126.2	Q9BX66-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7 link	c.3140G>T	p.Arg1047Leu	missense_variant	Exon 30 of 33	5	NM_001034954.3	ENSP00000360293.2		Q9BX66-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

218010

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417292

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698310

African (AFR)

AF:

0.00

AC:

AN:

32516

American (AMR)

AF:

0.00

AC:

AN:

41574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23338

East Asian (EAS)

AF:

0.00

AC:

AN:

39170

South Asian (SAS)

AF:

0.00

AC:

AN:

78690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086298

Other (OTH)

AF:

0.00

AC:

AN:

58404

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.3

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.83

T;T;T;.

M_CAP

Benign

0.023

MetaRNN

Benign

0.066

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

.;N;.;N

PhyloP100

-0.42

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.4

N;N;.;N

REVEL

Benign

0.0070

Sift

Uncertain

0.0050

D;D;.;D

Sift4G

Uncertain

0.019

D;D;.;D

Polyphen

0.081

B;B;.;B

Vest4

0.24

MutPred

0.28

.;Loss of glycosylation at P1046 (P = 0.0728);.;Loss of glycosylation at P1046 (P = 0.0728);

MVP

0.31

MPC

0.24

ClinPred

0.23

GERP RS

-1.7

PromoterAI

-0.0051

Neutral

(source)

Varity_R

0.068

gMVP

0.32

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over