rs35931910

Positions:

• chr15-84858449-C-G
• chr15-84858449-C-T

Variant summary

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

The NM_020778.5(ALPK3):​c.3711C>G​(p.Asp1237Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D1237D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALPK3 NM_020778.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.852

Genes affected

ALPK3 (HGNC:17574): (alpha kinase 3) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in cardiac muscle cell development. Predicted to be active in nucleus. Implicated in hypertrophic cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09912038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK3	NM_020778.5	c.3711C>G	p.Asp1237Glu	missense_variant	6/14	ENST00000258888.6	NP_065829.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK3	ENST00000258888.6	c.3711C>G	p.Asp1237Glu	missense_variant	6/14	1	NM_020778.5	ENSP00000258888	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000843 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.7
DANN	Benign	0.89
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.99	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.068
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.060	B
Vest4		0.11
MutPred		0.27		Loss of sheet (P = 0.0025);
MVP		0.62
MPC		0.11
ClinPred		0.084	T
GERP RS		3.2
Varity_R		0.12
gMVP		0.057

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

LitVar

Other links and lift over

dbSNP: rs35931910; hg19: chr15-85401680;