rs7054230

Positions:

• chrX-72599841-A-C
• chrX-72599841-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002637.4(PHKA1):​c.3072+2150T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PHKA1 NM_002637.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119754136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHKA1	NM_002637.4	c.3072+2150T>G		intron_variant		ENST00000373542.9	NP_002628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHKA1	ENST00000373542.9	c.3072+2150T>G		intron_variant		1	NM_002637.4	ENSP00000362643	P4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.1
DANN	Benign	0.44
DEOGEN2	Benign	0.0061	T;T
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.53	T
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	0.23	N;N
REVEL	Benign	0.14
Sift	Benign	0.52	T;T
Sift4G	Benign	0.62	T;T
Vest4		0.31
MutPred		0.31		.;Loss of stability (P = 0.0938);
MVP		0.62
ClinPred		0.043	T
GERP RS		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7054230; hg19: chrX-71819691;