rs1172336868

Variant names:

• chr10-95321967-C-G
• rs1172336868
• NM_001034954.3:c.3694G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-95321967-C-G
• chr10-95321967-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001034954.3(SORBS1):​c.3694G>C​(p.Asp1232His) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D1232N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SORBS1 NM_001034954.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3499089).

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.3694G>C	p.Asp1232His	missense	Exon 31 of 33	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.4702G>C	p.Asp1568His	missense	Exon 28 of 30	NP_001371381.1
	SORBS1	NM_001384448.1		c.4675G>C	p.Asp1559His	missense	Exon 27 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.3694G>C	p.Asp1232His	missense	Exon 31 of 33	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000361941.7	TSL:1	c.3694G>C	p.Asp1232His	missense	Exon 29 of 31	ENSP00000355136.3	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.3616G>C	p.Asp1206His	missense	Exon 30 of 32	ENSP00000360271.3	Q9BX66-11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251260 AF XY: 0.0000147

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461588 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 727118

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111780

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.0017	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PhyloP100		3.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.053	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.34		Gain of catalytic residue at D1232 (P = 0.0591)
MVP		0.67
MPC		0.68
ClinPred		0.85	D
GERP RS		6.1
Varity_R		0.30
gMVP		0.47
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1172336868; hg19: chr10-97081724;