chr10-104641362-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_014978.3(SORCS3):c.35G>A(p.Arg12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00482 in 1,408,960 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0048 ( 28 hom. )
Consequence
SORCS3
NM_014978.3 missense
NM_014978.3 missense
Scores
1
1
15
Clinical Significance
Conservation
PhyloP100: 1.29
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0037207603).
BP6
?
Variant 10-104641362-G-A is Benign according to our data. Variant chr10-104641362-G-A is described in ClinVar as [Benign]. Clinvar id is 721118.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SORCS3 | NM_014978.3 | c.35G>A | p.Arg12Lys | missense_variant | 1/27 | ENST00000369701.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SORCS3 | ENST00000369701.8 | c.35G>A | p.Arg12Lys | missense_variant | 1/27 | 1 | NM_014978.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00466 AC: 708AN: 151852Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00492 AC: 250AN: 50800Hom.: 1 AF XY: 0.00462 AC XY: 139AN XY: 30094
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GnomAD4 exome AF: 0.00484 AC: 6084AN: 1257000Hom.: 28 Cov.: 31 AF XY: 0.00471 AC XY: 2907AN XY: 616564
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GnomAD4 genome ? AF: 0.00466 AC: 708AN: 151960Hom.: 3 Cov.: 32 AF XY: 0.00509 AC XY: 378AN XY: 74290
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at