9-128946533-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014908.4(DOLK):c.771C>G(p.Ile257Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_014908.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DOLK | NM_014908.4 | c.771C>G | p.Ile257Met | missense_variant | Exon 1 of 1 | ENST00000372586.4 | NP_055723.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251370Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135872
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727242
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
DK1-congenital disorder of glycosylation Uncertain:1
This sequence change replaces isoleucine with methionine at codon 257 of the DOLK protein (p.Ile257Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs147416890, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. 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 tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at