10-95321967-C-T

Variant names:

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

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>A​(p.Asp1232Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SORBS1 NM_001034954.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.26861778).

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>A	p.Asp1232Asn	missense	Exon 31 of 33	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.4702G>A	p.Asp1568Asn	missense	Exon 28 of 30	NP_001371381.1
	SORBS1	NM_001384448.1		c.4675G>A	p.Asp1559Asn	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>A	p.Asp1232Asn	missense	Exon 31 of 33	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000361941.7	TSL:1	c.3694G>A	p.Asp1232Asn	missense	Exon 29 of 31	ENSP00000355136.3	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.3616G>A	p.Asp1206Asn	missense	Exon 30 of 32	ENSP00000360271.3	Q9BX66-11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.33	N
PhyloP100		3.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.093
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.28		Gain of MoRF binding (P = 0.0619)
MVP		0.67
MPC		0.36
ClinPred		0.77	D
GERP RS		6.1
Varity_R		0.17
gMVP		0.34
Mutation Taster		=65/35	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;