rs1025423127
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_002637.4(PHKA1):c.3631G>A(p.Val1211Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,209,496 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002637.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKA1 | NM_002637.4 | c.3631G>A | p.Val1211Met | missense_variant | 32/32 | ENST00000373542.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKA1 | ENST00000373542.9 | c.3631G>A | p.Val1211Met | missense_variant | 32/32 | 1 | NM_002637.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000268 AC: 3AN: 112015Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34173
GnomAD3 exomes AF: 0.00000552 AC: 1AN: 181188Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 66082
GnomAD4 exome AF: 0.0000219 AC: 24AN: 1097481Hom.: 0 Cov.: 29 AF XY: 0.0000193 AC XY: 7AN XY: 362849
GnomAD4 genome ? AF: 0.0000268 AC: 3AN: 112015Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34173
ClinVar
Submissions by phenotype
Glycogen storage disease IXd Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1211 of the PHKA1 protein (p.Val1211Met). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with PHKA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 465084). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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