Variant rs2074380 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_025144.4(ALPK1):c.2608G>A(p.Gly870Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,614,188 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0062 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 155 hom. )

Consequence

ALPK1
NM_025144.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029420257).

BP6

Variant 4-112432155-G-A is Benign according to our data. Variant chr4-112432155-G-A is described in ClinVar as [Benign]. Clinvar id is 2043714.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ALPK1	NM_025144.4 linkuse as main transcript	c.2608G>A	p.Gly870Ser	missense_variant	11/16	ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2 linkuse as main transcript	c.2608G>A	p.Gly870Ser	missense_variant	11/16		NP_001095876.1
ALPK1	NM_001253884.2 linkuse as main transcript	c.2374G>A	p.Gly792Ser	missense_variant	10/15		NP_001240813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1 linkuse as main transcript	c.2608G>A	p.Gly870Ser	missense_variant	11/16		NM_025144.4	ENSP00000498374	P1	Q96QP1-1

Frequencies

GnomAD3 genomes

AF:

0.00623

AC:

948

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0710

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.0414

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00851

AC:

2137

AN:

251122

Hom.:

AF XY:

0.00836

AC XY:

1135

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0620

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00384

AC:

5607

AN:

1461890

Hom.:

155

Cov.:

AF XY:

0.00380

AC XY:

2765

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.0756

Gnomad4 SAS exome

AF:

0.00255

Gnomad4 FIN exome

AF:

0.0311

Gnomad4 NFE exome

AF:

0.000305

Gnomad4 OTH exome

AF:

0.00500

GnomAD4 genome

AF:

0.00623

AC:

949

AN:

152298

Hom.:

Cov.:

AF XY:

0.00837

AC XY:

623

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0712

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.0414

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.00317

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00793

AC:

963

Asia WGS

AF:

0.0330

AC:

117

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.1

DANN

Benign

0.80

DEOGEN2

Benign

0.0040

.;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.68

T;T;.

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

.;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.16

N;N;N

REVEL

Benign

0.082

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.93

T;T;T

Polyphen

0.23

.;B;B

Vest4

0.19

MVP

0.25

MPC

0.088

ClinPred

0.0062

GERP RS

3.2

Varity_R

0.074

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over