rs28939087
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_018389.5(SLC35C1):c.439C>T(p.Arg147Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,298 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 Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R147H) has been classified as Uncertain significance.
Frequency
Consequence
NM_018389.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC35C1 | NM_018389.5 | c.439C>T | p.Arg147Cys | missense_variant | 1/2 | ENST00000314134.4 | |
SLC35C1 | NM_001145265.2 | c.400C>T | p.Arg134Cys | missense_variant | 2/3 | ||
SLC35C1 | NM_001145266.1 | c.400C>T | p.Arg134Cys | missense_variant | 2/3 | ||
SLC35C1 | XM_011520203.4 | c.439C>T | p.Arg147Cys | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC35C1 | ENST00000314134.4 | c.439C>T | p.Arg147Cys | missense_variant | 1/2 | 1 | NM_018389.5 | P4 | |
SLC35C1 | ENST00000442528.2 | c.400C>T | p.Arg134Cys | missense_variant | 2/3 | 1 | A1 | ||
SLC35C1 | ENST00000526817.2 | c.400C>T | p.Arg134Cys | missense_variant | 2/3 | 2 | A1 | ||
SLC35C1 | ENST00000530471.1 | c.400C>T | p.Arg134Cys | missense_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1456298Hom.: 0 Cov.: 35 AF XY: 0.00000276 AC XY: 2AN XY: 724696
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Leukocyte adhesion deficiency type II Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 15, 2021 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects SLC35C1 function (PMID: 11326279, 11326280, 16455955). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 4739). This missense change has been observed in individual(s) with congenital disorder of glycosylation (PMID: 11326279, 11326280). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 147 of the SLC35C1 protein (p.Arg147Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2001 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at