rs11726117

Positions:

• chr4-112432129-T-A
• chr4-112432129-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025144.4(ALPK1):​c.2582T>A​(p.Met861Lys) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M861T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALPK1 NM_025144.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

ALPK1 (HGNC:20917): (alpha kinase 1) This gene encodes an alpha kinase. Mice which were homozygous for disrupted copies of this gene exhibited coordination defects (PMID: 21208416). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ALPK1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03597477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK1	NM_025144.4	c.2582T>A	p.Met861Lys	missense_variant	11/16	ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2	c.2582T>A	p.Met861Lys	missense_variant	11/16		NP_001095876.1
ALPK1	NM_001253884.2	c.2348T>A	p.Met783Lys	missense_variant	10/15		NP_001240813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1	c.2582T>A	p.Met861Lys	missense_variant	11/16		NM_025144.4	ENSP00000498374.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.2
DANN	Benign	0.67
DEOGEN2	Benign	0.0010	.;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.33	T;T;.
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.036	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.0	.;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.060	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.97	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.078
MutPred		0.37		.;Loss of stability (P = 0.001);Loss of stability (P = 0.001);
MVP		0.10
MPC		0.14
ClinPred		0.13	T
GERP RS		1.7
Varity_R		0.13

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: rs11726117; hg19: chr4-113353285;