rs7082289

Variant names:

• chr10-106607262-C-T
• rs7082289
• NM_052918.5:c.3069G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_052918.5(SORCS1):​c.3069G>A​(p.Ala1023Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,766 control chromosomes in the GnomAD database, including 14,820 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2590 hom., cov: 32)
  • Exomes 𝑓: 0.11 (12230 hom.)
• Consequence: SORCS1 NM_052918.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.109).
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	NM_052918.5	MANE Select	c.3069G>A	p.Ala1023Ala	synonymous	Exon 23 of 26	NP_443150.3
	SORCS1	NM_001387556.1		c.3069G>A	p.Ala1023Ala	synonymous	Exon 23 of 27	NP_001374485.1
	SORCS1	NM_001013031.3		c.3069G>A	p.Ala1023Ala	synonymous	Exon 23 of 27	NP_001013049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.3069G>A	p.Ala1023Ala	synonymous	Exon 23 of 26	ENSP00000263054.5
	SORCS1	ENST00000369698.6	TSL:5	c.1800G>A	p.Ala600Ala	synonymous	Exon 15 of 19	ENSP00000358712.2
	SORCS1	ENST00000452214.5	TSL:3	c.111G>A	p.Ala37Ala	synonymous	Exon 2 of 6	ENSP00000407769.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23765 AN: 151958 Hom.: 2590 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0828

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.140 AC: 34977 AN: 250572 AF XY: 0.146

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.0840

Gnomad ASJ exome AF: 0.0840

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0850

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.109 AC: 158690 AN: 1461690 Hom.: 12230 Cov.: 32 AF XY: 0.114 AC XY: 83191 AN XY: 727140

African (AFR) AF: 0.293 AC: 9808 AN: 33472

American (AMR) AF: 0.0849 AC: 3796 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 2206 AN: 26136

East Asian (EAS) AF: 0.219 AC: 8703 AN: 39672

South Asian (SAS) AF: 0.317 AC: 27358 AN: 86240

European-Finnish (FIN) AF: 0.101 AC: 5383 AN: 53380

Middle Eastern (MID) AF: 0.126 AC: 726 AN: 5768

European-Non Finnish (NFE) AF: 0.0838 AC: 93151 AN: 1111922

Other (OTH) AF: 0.125 AC: 7559 AN: 60388

GnomAD4 genome AF: 0.156 AC: 23773 AN: 152076 Hom.: 2590 Cov.: 32 AF XY: 0.159 AC XY: 11850 AN XY: 74330

African (AFR) AF: 0.283 AC: 11730 AN: 41466

American (AMR) AF: 0.106 AC: 1618 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0828 AC: 287 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1220 AN: 5130

South Asian (SAS) AF: 0.331 AC: 1596 AN: 4824

European-Finnish (FIN) AF: 0.0991 AC: 1050 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5913 AN: 67982

Other (OTH) AF: 0.143 AC: 301 AN: 2110

Alfa AF: 0.109 Hom.: 1156

Bravo AF: 0.157

Asia WGS AF: 0.286 AC: 993 AN: 3478

EpiCase AF: 0.0904

EpiControl AF: 0.0869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.027
DANN	Benign	0.42
PhyloP100		-2.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs7082289; hg19: chr10-108367020; COSMIC: COSV53862637; COSMIC: COSV53862637;