4-112377879-C-A

Variant names:

• chr4-112377879-C-A
• rs543243733
• NM_025144.4:c.102C>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_025144.4(ALPK1):​c.102C>A​(p.Ser34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 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. S34S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ALPK1 NM_025144.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03170514).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPK1	NM_025144.4	c.102C>A	p.Ser34Arg	missense_variant	Exon 3 of 16	ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2	c.102C>A	p.Ser34Arg	missense_variant	Exon 3 of 16		NP_001095876.1
ALPK1	NM_001253884.2	c.23C>A	p.Ala8Glu	missense_variant	Exon 3 of 15		NP_001240813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1	c.102C>A	p.Ser34Arg	missense_variant	Exon 3 of 16		NM_025144.4	ENSP00000498374.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460512 Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7 AN XY: 726366

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000328

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.0010
DANN	Benign	0.52
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.072
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.21	T
Vest4		0.13
MutPred		0.20		Gain of glycosylation at T6 (P = 0.0061);
MVP		0.12
ClinPred		0.037	T
GERP RS		-12

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: rs543243733; hg19: chr4-113299035;