rs1490173

Variant names:

• chr10-104726336-G-A
• rs1490173
• NM_014978.3:c.627+84382G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-104726336-G-A
• chr10-104726336-G-C
• chr10-104726336-G-T

Variant summary

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

The NM_014978.3(SORCS3):​c.627+84382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,014 control chromosomes in the GnomAD database, including 9,257 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 0.34 (9257 hom., cov: 32)
• Consequence: SORCS3 NM_014978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 1 publications found

Genes affected

SORCS3 (HGNC:16699): (sortilin related VPS10 domain containing receptor 3) This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. [provided by RefSeq, Dec 2014]

SORCS3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS3	NM_014978.3	c.627+84382G>A		intron_variant	Intron 1 of 26	ENST00000369701.8	NP_055793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS3	ENST00000369701.8	c.627+84382G>A		intron_variant	Intron 1 of 26	1	NM_014978.3	ENSP00000358715.3

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51142 AN: 151896 Hom.: 9242 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.337 AC: 51190 AN: 152014 Hom.: 9257 Cov.: 32 AF XY: 0.340 AC XY: 25238 AN XY: 74308

African (AFR) AF: 0.435 AC: 18025 AN: 41450

American (AMR) AF: 0.270 AC: 4127 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3466

East Asian (EAS) AF: 0.635 AC: 3274 AN: 5158

South Asian (SAS) AF: 0.333 AC: 1604 AN: 4822

European-Finnish (FIN) AF: 0.330 AC: 3491 AN: 10566

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18372 AN: 67958

Other (OTH) AF: 0.340 AC: 719 AN: 2114

Alfa AF: 0.296 Hom.: 1089

Bravo AF: 0.342

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.74
PhyloP100		-0.13
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: rs1490173; hg19: chr10-106486094;