chr17-75758563-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000154.2(GALK1):c.830G>A(p.Arg277Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,596,756 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R277W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000154.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALK1 | NM_000154.2 | c.830G>A | p.Arg277Gln | missense_variant | 6/8 | ENST00000588479.6 | |
GALK1 | NM_001381985.1 | c.830G>A | p.Arg277Gln | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALK1 | ENST00000588479.6 | c.830G>A | p.Arg277Gln | missense_variant | 6/8 | 1 | NM_000154.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000453 AC: 10AN: 220888Hom.: 0 AF XY: 0.0000654 AC XY: 8AN XY: 122374
GnomAD4 exome AF: 0.0000166 AC: 24AN: 1444418Hom.: 0 Cov.: 34 AF XY: 0.0000167 AC XY: 12AN XY: 718476
GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74496
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 05, 2022 | Variant summary: GALK1 c.830G>A (p.Arg277Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.5e-05 in 220888 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in GALK1 causing Deficiency Of Galactokinase (4.5e-05 vs 0.0011), allowing no conclusion about variant significance. c.830G>A has been reported in the literature as a compound heterozygous genotype in at-least one individual affected with Deficiency Of Galactokinase (example, Doo Park_2007). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function (example, Doo Park_2007). The most pronounced variant effect results in approximately 10%-15% of normal GALK activity in vitro. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. - |
Deficiency of galactokinase Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 23, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at