rs144211929

Variant names:

• chr16-47511750-A-C
• NM_000293.3:c.491A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-47511750-A-C
• chr16-47511750-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000293.3(PHKB):​c.491A>C​(p.Tyr164Ser) variant causes a missense 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. 13/21 in silico tools predict 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: 32)
• Consequence: PHKB NM_000293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

Genes affected

PHKB (HGNC:8927): (phosphorylase kinase regulatory subunit beta) 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, encoded by two different genes. The beta subunit is the same in both the muscle and hepatic isoforms, encoded by this gene, which is a member of the phosphorylase b kinase regulatory subunit family. The gamma subunit also includes the skeletal muscle and hepatic isoforms, 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 9B, also known as phosphorylase kinase deficiency of liver and muscle. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. Two pseudogenes have been found on chromosomes 14 and 20, respectively.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2697943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHKB	NM_000293.3	c.491A>C	p.Tyr164Ser	missense_variant	Exon 5 of 31	ENST00000323584.10	NP_000284.1
PHKB	NM_001363837.1	c.491A>C	p.Tyr164Ser	missense_variant	Exon 5 of 31		NP_001350766.1
PHKB	NM_001031835.3	c.470A>C	p.Tyr157Ser	missense_variant	Exon 6 of 32		NP_001027005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHKB	ENST00000323584.10	c.491A>C	p.Tyr164Ser	missense_variant	Exon 5 of 31	1	NM_000293.3	ENSP00000313504.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.16	.;.;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.017
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.9	.;.;M;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.5	N;N;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.033	D;T;T;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.086, 0.035	.;B;.;B
Vest4		0.47, 0.47, 0.46
MutPred		0.41		.;.;Gain of disorder (P = 0.0057);Gain of disorder (P = 0.0057);
MVP		0.90
MPC		0.17
ClinPred		0.70	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-47545661;