10-104851510-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014978.3(SORCS3):​c.695+8651G>A variant causes a intron change. The variant allele was found at a frequency of 0.732 in 151,834 control chromosomes in the GnomAD database, including 41,671 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 0.73 ( 41671 hom., cov: 32)

Consequence

SORCS3
NM_014978.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SORCS3NM_014978.3 linkuse as main transcriptc.695+8651G>A intron_variant ENST00000369701.8 NP_055793.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SORCS3ENST00000369701.8 linkuse as main transcriptc.695+8651G>A intron_variant 1 NM_014978.3 ENSP00000358715 P1

Frequencies

GnomAD3 genomes
AF:
0.732
AC:
111114
AN:
151716
Hom.:
41624
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.881
Gnomad AMI
AF:
0.759
Gnomad AMR
AF:
0.739
Gnomad ASJ
AF:
0.749
Gnomad EAS
AF:
0.857
Gnomad SAS
AF:
0.579
Gnomad FIN
AF:
0.727
Gnomad MID
AF:
0.712
Gnomad NFE
AF:
0.641
Gnomad OTH
AF:
0.735
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.732
AC:
111210
AN:
151834
Hom.:
41671
Cov.:
32
AF XY:
0.733
AC XY:
54354
AN XY:
74168
show subpopulations
Gnomad4 AFR
AF:
0.882
Gnomad4 AMR
AF:
0.738
Gnomad4 ASJ
AF:
0.749
Gnomad4 EAS
AF:
0.856
Gnomad4 SAS
AF:
0.578
Gnomad4 FIN
AF:
0.727
Gnomad4 NFE
AF:
0.641
Gnomad4 OTH
AF:
0.730
Alfa
AF:
0.669
Hom.:
32908
Bravo
AF:
0.747
Asia WGS
AF:
0.701
AC:
2440
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
18
DANN
Benign
0.33

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1021362; hg19: chr10-106611268; API