X-72695733-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_002637.4(PHKA1):​c.429C>G​(p.Leu143Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,096,478 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)
Exomes š‘“: 0.0000018 ( 0 hom. 0 hem. )

Consequence

PHKA1
NM_002637.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.717
Variant links:
Genes affected
PHKA1 (HGNC:8925): (phosphorylase kinase regulatory subunit alpha 1) Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, and the skeletal muscle isoform is encoded by this gene. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, which are encoded by two different genes. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9D, also known as X-linked muscle glycogenosis. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. A pseudogene has been found on chromosome 1.[provided by RefSeq, Feb 2010]
PHKA1-AS1 (HGNC:40446): (PHKA1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP7
Synonymous conserved (PhyloP=0.717 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHKA1NM_002637.4 linkc.429C>G p.Leu143Leu synonymous_variant Exon 4 of 32 ENST00000373542.9 NP_002628.2 P46020-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHKA1ENST00000373542.9 linkc.429C>G p.Leu143Leu synonymous_variant Exon 4 of 32 1 NM_002637.4 ENSP00000362643.4 P46020-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1096478
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
362630
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000238
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
5.0
DANN
Benign
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-71915583; API