rs193920900

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-95337020-C-G
• chr10-95337020-C-T
• chr10-95337020-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034954.3(SORBS1):​c.3140G>C​(p.Arg1047Pro) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1047Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SORBS1 NM_001034954.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07439396).

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>C	p.Arg1047Pro	missense	Exon 30 of 33	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.4016G>C	p.Arg1339Pro	missense	Exon 27 of 30	NP_001371381.1
	SORBS1	NM_001384448.1		c.3989G>C	p.Arg1330Pro	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>C	p.Arg1047Pro	missense	Exon 30 of 33	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000361941.7	TSL:1	c.3140G>C	p.Arg1047Pro	missense	Exon 28 of 31	ENSP00000355136.3	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.3002G>C	p.Arg1001Pro	missense	Exon 28 of 32	ENSP00000360271.3	Q9BX66-11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.85
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.42
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.016
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.016	D
Polyphen		0.47	P
Vest4		0.48
MutPred		0.24		Gain of catalytic residue at P1046 (P = 0.0186)
MVP		0.35
MPC		0.34
ClinPred		0.15	T
GERP RS		-1.7
PromoterAI		-0.040	Neutral
Varity_R		0.17
gMVP		0.30
Mutation Taster		=97/3	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; COSMIC: COSV53361507; COSMIC: COSV53361507;