chrX-18893592-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PP3_Strong
The NM_000292.3(PHKA2):āc.3601T>Cā(p.Tyr1201His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,556 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000292.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKA2 | NM_000292.3 | c.3601T>C | p.Tyr1201His | missense_variant | 33/33 | ENST00000379942.5 | |
PHKA2-AS1 | NR_029379.1 | n.467+254A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKA2 | ENST00000379942.5 | c.3601T>C | p.Tyr1201His | missense_variant | 33/33 | 1 | NM_000292.3 | P1 | |
PHKA2-AS1 | ENST00000452900.5 | n.467+254A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 182993Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67587
GnomAD4 exome AF: 0.00000638 AC: 7AN: 1097556Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 1AN XY: 362922
GnomAD4 genome Cov.: 24
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 | Oct 11, 2021 | Variant summary: PHKA2 c.3601T>C (p.Tyr1201His) 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 5.5e-06 in 182993 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3601T>C has been reported in the literature as a non-informative genotype (second allele not specified) in at-least one individual affected with GSD type IX (Glycogen Phosphorylase Kinase Deficiency) (example, Brown_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Glycogen Phosphorylase Kinase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at