Variant chr10-106579388-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000263054.11(SORCS1):c.3352G>A(p.Val1118Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,613,890 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 7 hom. )

Consequence

SORCS1
ENST00000263054.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

SORCS1 (HGNC:16697): (sortilin related VPS10 domain containing receptor 1) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. Two of the five family members (sortilin and sortilin-related receptor) are synthesized as preproproteins; it is not yet known if this encoded protein is also a preproprotein. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

SORCS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008796275).

BP6

Variant 10-106579388-C-T is Benign according to our data. Variant chr10-106579388-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640821.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5 linkuse as main transcript	c.3352G>A	p.Val1118Ile	missense_variant	25/26	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11 linkuse as main transcript	c.3352G>A	p.Val1118Ile	missense_variant	25/26	1	NM_052918.5	ENSP00000263054	P1	Q8WY21-1
SORCS1	ENST00000369698.6 linkuse as main transcript	c.2086G>A	p.Val696Ile	missense_variant	17/19	5		ENSP00000358712
SORCS1	ENST00000452214.5 linkuse as main transcript	c.397G>A	p.Val133Ile	missense_variant	4/6	3		ENSP00000407769
SORCS1	ENST00000473866.1 linkuse as main transcript	n.240G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00229

Gnomad FIN

AF:

0.00586

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00162

AC:

406

AN:

250452

Hom.:

AF XY:

0.00177

AC XY:

239

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00327

Gnomad FIN exome

AF:

0.00531

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00114

AC:

1673

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

922

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00321

Gnomad4 FIN exome

AF:

0.00532

Gnomad4 NFE exome

AF:

0.000939

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00118

AC:

179

AN:

152086

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

103

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00250

Gnomad4 FIN

AF:

0.00586

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000654

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00166

AC:

201

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SORCS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.29

DEOGEN2

Benign

0.058

T;.;T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0088

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.67

N;.;.;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.64

N;.;.;N;.

REVEL

Benign

0.080

Sift

Benign

0.95

T;.;.;T;.

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.012

B;.;.;.;.

Vest4

0.33

MVP

0.10

MPC

0.21

ClinPred

0.028

GERP RS

5.9

Varity_R

0.058

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over