rs10491050

Variant names:

• chr10-106576250-T-C
• rs10491050
• NM_052918.5:c.*1170A>G

Variant summary

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

The NM_052918.5(SORCS1):​c.*1170A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152,630 control chromosomes in the GnomAD database, including 506 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 0.050 (505 hom., cov: 33)
  • Exomes 𝑓: 0.018 (1 hom.)
• Consequence: SORCS1 NM_052918.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 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.*1170A>G		3_prime_UTR	Exon 26 of 26	NP_443150.3
	SORCS1	NM_001013031.3		c.*971A>G		3_prime_UTR	Exon 27 of 27	NP_001013049.1
	SORCS1	NM_001206572.2		c.*1298A>G		3_prime_UTR	Exon 27 of 27	NP_001193501.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.*1170A>G		3_prime_UTR	Exon 26 of 26	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7513 AN: 152056 Hom.: 494 Cov.: 33

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00682

Gnomad OTH AF: 0.0479

GnomAD4 exome AF: 0.0175 AC: 8 AN: 456 Hom.: 1 Cov.: 0 AF XY: 0.0112 AC XY: 4 AN XY: 358

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.417 AC: 5 AN: 12

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 388

Other (OTH) AF: 0.0455 AC: 1 AN: 22

GnomAD4 genome AF: 0.0495 AC: 7534 AN: 152174 Hom.: 505 Cov.: 33 AF XY: 0.0554 AC XY: 4122 AN XY: 74400

African (AFR) AF: 0.0523 AC: 2172 AN: 41518

American (AMR) AF: 0.162 AC: 2475 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1280 AN: 5166

South Asian (SAS) AF: 0.0721 AC: 347 AN: 4814

European-Finnish (FIN) AF: 0.0530 AC: 562 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00682 AC: 464 AN: 67994

Other (OTH) AF: 0.0488 AC: 103 AN: 2110

Alfa AF: 0.0299 Hom.: 425

Bravo AF: 0.0600

Asia WGS AF: 0.140 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.037
DANN	Benign	0.57
PhyloP100		-1.4
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: rs10491050; hg19: chr10-108336008;