rs12359404

Positions:

• chr10-106574431-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052918.5(SORCS1):​c.*2989G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 152,582 control chromosomes in the GnomAD database, including 193 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 0.041 (193 hom., cov: 32)
  • Exomes 𝑓: 0.026 (0 hom.)
• Consequence: SORCS1 NM_052918.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.*2989G>A		3_prime_UTR_variant	26/26	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.*2989G>A		3_prime_UTR_variant	26/26	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.0408 AC: 6197 AN: 152004 Hom.: 192 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0397

GnomAD4 exome AF: 0.0261 AC: 12 AN: 460 Hom.: 0 Cov.: 0 AF XY: 0.0393 AC XY: 11 AN XY: 280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0280

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0408 AC: 6208 AN: 152122 Hom.: 193 Cov.: 32 AF XY: 0.0425 AC XY: 3159 AN XY: 74350

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.0206

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0239 Hom.: 58

Bravo AF: 0.0393

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.022
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs12359404; hg19: chr10-108334189;