10-95336741-G-C

Variant names:

• chr10-95336741-G-C
• NM_001034954.3:c.3419C>G

Variant summary

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

The NM_001034954.3(SORBS1):​c.3419C>G​(p.Pro1140Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SORBS1 NM_001034954.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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=0.12012136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.3419C>G	p.Pro1140Arg	missense_variant	Exon 30 of 33	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.3419C>G	p.Pro1140Arg	missense_variant	Exon 30 of 33	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727228

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: 0.00000180

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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;.;T;.;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.86	D;D;D;D;.;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	.;.;N;.;N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N;D;N;.;N;D
REVEL	Benign	0.047
Sift	Uncertain	0.0060	D;T;D;.;D;T
Sift4G	Uncertain	0.011	D;D;D;.;D;D
Polyphen		0.70	P;P;P;.;P;P
Vest4		0.18
MutPred		0.34		.;.;Gain of MoRF binding (P = 7e-04);.;Gain of MoRF binding (P = 7e-04);.;
MVP		0.57
MPC		0.60
ClinPred		0.31	T
GERP RS		2.7
Varity_R		0.096
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-97096498;