rs139132974

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052918.5(SORCS1):ā€‹c.3352G>Cā€‹(p.Val1118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SORCS1
NM_052918.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10572764).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SORCS1NM_052918.5 linkc.3352G>C p.Val1118Leu missense_variant Exon 25 of 26 ENST00000263054.11 NP_443150.3 Q8WY21-1B3KWN9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SORCS1ENST00000263054.11 linkc.3352G>C p.Val1118Leu missense_variant Exon 25 of 26 1 NM_052918.5 ENSP00000263054.5 Q8WY21-1
SORCS1ENST00000369698.6 linkc.2083G>C p.Val695Leu missense_variant Exon 17 of 19 5 ENSP00000358712.2 X6R7D6
SORCS1ENST00000452214.5 linkc.394G>C p.Val132Leu missense_variant Exon 4 of 6 3 ENSP00000407769.1 H7C2U3
SORCS1ENST00000473866.1 linkn.240G>C non_coding_transcript_exon_variant Exon 3 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250452
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135402
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461804
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Benign
0.66
DEOGEN2
Benign
0.070
T;.;T;.;.
Eigen
Benign
-0.18
Eigen_PC
Benign
0.051
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.84
T;T;T;T;T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L;.;.;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
0.45
N;.;.;N;.
REVEL
Benign
0.076
Sift
Benign
0.91
T;.;.;T;.
Sift4G
Benign
0.83
T;T;T;T;T
Polyphen
0.0020
B;.;.;.;.
Vest4
0.35
MutPred
0.32
Loss of sheet (P = 0.0228);.;.;.;.;
MVP
0.068
MPC
0.25
ClinPred
0.19
T
GERP RS
5.9
Varity_R
0.090
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs139132974; hg19: chr10-108339146; API