rs7084834

chr10-104643451-C-T

Variant summary

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

The NM_014978.3(SORCS3):c.627+1497C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,156 control chromosomes in the GnomAD database, including 48,159 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 0.79 (48159 hom., cov: 32)
• Consequence: SORCS3 NM_014978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS3	NM_014978.3	c.627+1497C>T		intron_variant		ENST00000369701.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS3	ENST00000369701.8	c.627+1497C>T		intron_variant		1	NM_014978.3	P1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120384 AN: 152040 Hom.: 48135 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.792 AC: 120446 AN: 152156 Hom.: 48159 Cov.: 32 AF XY: 0.791 AC XY: 58874 AN XY: 74386

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.797

Alfa AF: 0.824 Hom.: 22433

Bravo AF: 0.778

Asia WGS AF: 0.652 AC: 2272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.97
Dann	Benign	0.85

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: rs7084834; hg19: chr10-106403209;