10-107126535-G-T

Variant names:

• chr10-107126535-G-T
• rs596577
• NM_052918.5:c.558+37434C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387556.1(SORCS1):​c.558+37434C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,012 control chromosomes in the GnomAD database, including 10,593 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 0.32 (10593 hom., cov: 32)
• Consequence: SORCS1 NM_001387556.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387556.1. 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.558+37434C>A		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.558+37434C>A		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.558+37434C>A		intron	N/A	NP_001013049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.558+37434C>A		intron	N/A	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47826 AN: 151894 Hom.: 10557 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.315 AC: 47918 AN: 152012 Hom.: 10593 Cov.: 32 AF XY: 0.313 AC XY: 23267 AN XY: 74310

African (AFR) AF: 0.630 AC: 26131 AN: 41454

American (AMR) AF: 0.227 AC: 3476 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3464

East Asian (EAS) AF: 0.411 AC: 2119 AN: 5158

South Asian (SAS) AF: 0.205 AC: 987 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2084 AN: 10560

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

European-Non Finnish (NFE) AF: 0.173 AC: 11765 AN: 67964

Other (OTH) AF: 0.254 AC: 534 AN: 2104

Alfa AF: 0.195 Hom.: 6198

Bravo AF: 0.335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.49
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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: rs596577; hg19: chr10-108886293;