rs137852546
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 12P and 1B. PVS1_ModeratePP3_ModeratePP5_Very_StrongBS2_Supporting
The NM_002637.4(PHKA1):c.3334G>T(p.Glu1112Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000075 in 1,200,593 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_002637.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKA1 | NM_002637.4 | c.3334G>T | p.Glu1112Ter | stop_gained | 31/32 | ENST00000373542.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKA1 | ENST00000373542.9 | c.3334G>T | p.Glu1112Ter | stop_gained | 31/32 | 1 | NM_002637.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000269 AC: 3AN: 111576Hom.: 0 Cov.: 23 AF XY: 0.0000592 AC XY: 2AN XY: 33772
GnomAD4 exome AF: 0.00000551 AC: 6AN: 1089017Hom.: 0 Cov.: 28 AF XY: 0.00000564 AC XY: 2AN XY: 354779
GnomAD4 genome ? AF: 0.0000269 AC: 3AN: 111576Hom.: 0 Cov.: 23 AF XY: 0.0000592 AC XY: 2AN XY: 33772
ClinVar
Submissions by phenotype
Glycogen storage disease IXd Pathogenic:3
Pathogenic, criteria provided, single submitter | research | Duke University Health System Sequencing Clinic, Duke University Health System | Apr 20, 2023 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1994 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | This sequence change creates a premature translational stop signal (p.Glu1112*) in the PHKA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHKA1 are known to be pathogenic (PMID: 9731190, 15637709). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of PHKA1-related conditions (PMID: 7874115). ClinVar contains an entry for this variant (Variation ID: 9923). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at