rs1368327754
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_052918.5(SORCS1):c.2621G>T(p.Ser874Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,218 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Consequence
SORCS1
NM_052918.5 missense
NM_052918.5 missense
Scores
1
11
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.48
Genes affected
SORCS1 (HGNC:16697): (sortilin related VPS10 domain containing receptor 1) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. Two of the five family members (sortilin and sortilin-related receptor) are synthesized as preproproteins; it is not yet known if this encoded protein is also a preproprotein. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SORCS1 | ENST00000263054.11 | c.2621G>T | p.Ser874Ile | missense_variant | Exon 19 of 26 | 1 | NM_052918.5 | ENSP00000263054.5 | ||
| SORCS1 | ENST00000369698.6 | c.1352G>T | p.Ser451Ile | missense_variant | Exon 11 of 19 | 5 | ENSP00000358712.2 | |||
| SORCS1 | ENST00000486192.1 | n.147G>T | non_coding_transcript_exon_variant | Exon 1 of 2 | 2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33
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GnomAD4 exome Cov.: 31
GnomAD4 exome
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31
GnomAD4 genome 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74370
GnomAD4 genome
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;.;N;.
REVEL
Uncertain
Sift
Benign
T;.;.;T;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.0019);.;.;.;.;
MVP
MPC
0.57
ClinPred
D
GERP RS
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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