10-95337020-C-A

Variant names:

• chr10-95337020-C-A
• rs193920900
• NM_001034954.3:c.3140G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 3 publications found

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

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034954.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	NM_001034954.3	MANE Select	c.3140G>T	p.Arg1047Leu	missense	Exon 30 of 33	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.4016G>T	p.Arg1339Leu	missense	Exon 27 of 30	NP_001371381.1
	SORBS1	NM_001384448.1		c.3989G>T	p.Arg1330Leu	missense	Exon 26 of 29	NP_001371377.1	A0A3B3IRW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.3140G>T	p.Arg1047Leu	missense	Exon 30 of 33	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000361941.7	TSL:1	c.3140G>T	p.Arg1047Leu	missense	Exon 28 of 31	ENSP00000355136.3	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.3002G>T	p.Arg1001Leu	missense	Exon 28 of 32	ENSP00000360271.3	Q9BX66-11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 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: 0 AN: 1417292 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 698310

African (AFR) AF: 0.00 AC: 0 AN: 32516

American (AMR) AF: 0.00 AC: 0 AN: 41574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23338

East Asian (EAS) AF: 0.00 AC: 0 AN: 39170

South Asian (SAS) AF: 0.00 AC: 0 AN: 78690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5570

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086298

Other (OTH) AF: 0.00 AC: 0 AN: 58404

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.42
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.0070
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.019	D
Polyphen		0.081	B
Vest4		0.24
MutPred		0.28		Loss of glycosylation at P1046 (P = 0.0728)
MVP		0.31
MPC		0.24
ClinPred		0.23	T
GERP RS		-1.7
PromoterAI		-0.0051	Neutral
Varity_R		0.068
gMVP		0.32
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs193920900; hg19: chr10-97096777;