10-106576250-T-C

Position:

• chr10-106576250-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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	UniProt
SORCS1	NM_052918.5	c.*1170A>G		3_prime_UTR_variant	26/26	ENST00000263054.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS1	ENST00000263054.11	c.*1170A>G		3_prime_UTR_variant	26/26	1	NM_052918.5	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0455

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

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.0721

Gnomad4 FIN AF: 0.0530

Gnomad4 NFE AF: 0.00682

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0268 Hom.: 321

Bravo AF: 0.0600

Asia WGS AF: 0.140 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.037
DANN	Benign	0.57

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: rs10491050; hg19: chr10-108336008;