Variant 10-106579159-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001387556.1(SORCS1):c.3464A>G(p.Asn1155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,614,072 control chromosomes in the GnomAD database, including 2,201 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.039 ( 315 hom., cov: 32)

Exomes 𝑓: 0.019 ( 1886 hom. )

Consequence

SORCS1
NM_001387556.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0930

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:

SORCS1 (HGNC:):

SORCS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029719472).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5 linkuse as main transcript	c.3371+210A>G		intron_variant		ENST00000263054.11	NP_443150.3	Q8WY21-1B3KWN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SORCS1	ENST00000263054.11 linkuse as main transcript	c.3371+210A>G		intron_variant		1	NM_052918.5	ENSP00000263054.5	Q8WY21-1
SORCS1	ENST00000369698.6 linkuse as main transcript	c.2195A>G	p.Asn732Ser	missense_variant	18/19	5		ENSP00000358712.2	X6R7D6
SORCS1	ENST00000452214.5 linkuse as main transcript	c.506A>G	p.Asn169Ser	missense_variant	5/6	3		ENSP00000407769.1	H7C2U3
SORCS1	ENST00000473866.1 linkuse as main transcript	n.352A>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.0390

AC:

5932

AN:

152116

Hom.:

315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0513

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0955

Gnomad ASJ

AF:

0.0306

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.0717

Gnomad FIN

AF:

0.0362

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00225

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0513

AC:

12905

AN:

251332

Hom.:

998

AF XY:

0.0468

AC XY:

6352

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.257

Gnomad SAS exome

AF:

0.0572

Gnomad FIN exome

AF:

0.0299

Gnomad NFE exome

AF:

0.00258

Gnomad OTH exome

AF:

0.0325

GnomAD4 exome

AF:

0.0187

AC:

27301

AN:

1461836

Hom.:

1886

Cov.:

AF XY:

0.0191

AC XY:

13917

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0510

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.0303

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.0567

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.0293

GnomAD4 genome

AF:

0.0390

AC:

5936

AN:

152236

Hom.:

315

Cov.:

AF XY:

0.0436

AC XY:

3249

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0513

Gnomad4 AMR

AF:

0.0956

Gnomad4 ASJ

AF:

0.0306

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.0718

Gnomad4 FIN

AF:

0.0362

Gnomad4 NFE

AF:

0.00223

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0103

Hom.:

179

Bravo

AF:

0.0439

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.0572

AC:

252

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.0457

AC:

5555

Asia WGS

AF:

0.135

AC:

467

AN:

3478

EpiCase

AF:

0.00245

EpiControl

AF:

0.00267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.9

DANN

Benign

0.67

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.32

.;N;.

REVEL

Benign

0.062

Sift

Benign

0.28

.;T;.

Sift4G

Benign

0.43

T;T;T

Vest4

0.027

MPC

0.20

ClinPred

0.0034

GERP RS

-6.6

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over