rs193920991
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_052918.5(SORCS1):c.3371+126C>T variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
SORCS1
NM_052918.5 intron
NM_052918.5 intron
Scores
3
5
5
Clinical Significance
Conservation
PhyloP100: 9.60
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.776
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SORCS1 | NM_052918.5 | c.3371+126C>T | intron_variant | ENST00000263054.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SORCS1 | ENST00000263054.11 | c.3371+126C>T | intron_variant | 1 | NM_052918.5 | P1 | |||
SORCS1 | ENST00000369698.6 | c.2114C>T | p.Pro705Leu | missense_variant | 18/19 | 5 | |||
SORCS1 | ENST00000452214.5 | c.425C>T | p.Pro142Leu | missense_variant | 5/6 | 3 | |||
SORCS1 | ENST00000473866.1 | n.268C>T | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152032Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000717 AC: 18AN: 251148Hom.: 0 AF XY: 0.0000958 AC XY: 13AN XY: 135720
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GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727214
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GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152032Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74256
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D;D
Vest4
0.88
MVP
MPC
0.90
ClinPred
D
GERP RS
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