chrX-72695716-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002637.4(PHKA1):c.446C>T(p.Thr149Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. T149A) has been classified as Uncertain significance.
Frequency
Consequence
NM_002637.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKA1 | NM_002637.4 | c.446C>T | p.Thr149Ile | missense_variant | 4/32 | ENST00000373542.9 | |
PHKA1-AS1 | NR_110391.1 | n.55-1443G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKA1 | ENST00000373542.9 | c.446C>T | p.Thr149Ile | missense_variant | 4/32 | 1 | NM_002637.4 | P4 | |
PHKA1-AS1 | ENST00000420998.1 | n.54-1443G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000365 AC: 4AN: 1096309Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 362569
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
Glycogen storage disease IXd Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 09, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PHKA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 149 of the PHKA1 protein (p.Thr149Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.