rs3011669

Variant names:

• chr10-105252415-A-G
• rs3011669
• NM_014978.3:c.3106-360A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-105252415-A-G
• chr10-105252415-A-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.3106-360A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,034 control chromosomes in the GnomAD database, including 25,182 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 0.57 (25182 hom., cov: 33)
• Consequence: SORCS3 NM_014978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 2 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS3	NM_014978.3	c.3106-360A>G		intron_variant	Intron 22 of 26	ENST00000369701.8	NP_055793.1
SORCS3	XM_011539542.2	c.2038-360A>G		intron_variant	Intron 18 of 22		XP_011537844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS3	ENST00000369701.8	c.3106-360A>G		intron_variant	Intron 22 of 26	1	NM_014978.3	ENSP00000358715.3

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86976 AN: 151916 Hom.: 25177 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.572 AC: 87012 AN: 152034 Hom.: 25182 Cov.: 33 AF XY: 0.576 AC XY: 42853 AN XY: 74334

African (AFR) AF: 0.593 AC: 24551 AN: 41420

American (AMR) AF: 0.508 AC: 7773 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2160 AN: 3468

East Asian (EAS) AF: 0.749 AC: 3867 AN: 5166

South Asian (SAS) AF: 0.505 AC: 2435 AN: 4824

European-Finnish (FIN) AF: 0.677 AC: 7153 AN: 10570

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37345 AN: 67984

Other (OTH) AF: 0.563 AC: 1190 AN: 2112

Alfa AF: 0.548 Hom.: 11377

Bravo AF: 0.564

Asia WGS AF: 0.543 AC: 1890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.2
DANN	Benign	0.74
PhyloP100		-0.0090
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: rs3011669; hg19: chr10-107012173;