19-17555753-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_024656.4(COLGALT1):c.40C>T(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000568 in 1,214,916 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. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024656.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COLGALT1 | NM_024656.4 | c.40C>T | p.Pro14Ser | missense_variant | Exon 1 of 12 | ENST00000252599.9 | NP_078932.2 | |
COLGALT1 | XM_005260080.5 | c.-783C>T | upstream_gene_variant | XP_005260137.1 | ||||
NIBAN3 | XM_011527786.3 | c.*594C>T | downstream_gene_variant | XP_011526088.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000331 AC: 50AN: 151268Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.0000169 AC: 18AN: 1063540Hom.: 0 Cov.: 29 AF XY: 0.0000179 AC XY: 9AN XY: 502694
GnomAD4 genome AF: 0.000337 AC: 51AN: 151376Hom.: 0 Cov.: 31 AF XY: 0.000324 AC XY: 24AN XY: 73984
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 14 of the COLGALT1 protein (p.Pro14Ser). This variant is present in population databases (no rsID available, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with COLGALT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1973108). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at