Variant rs2074381 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.2746A>G(p.Asn916Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,614,202 control chromosomes in the GnomAD database, including 163 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: 0.0037 ( 143 hom. )

Consequence

ALPK1
NM_025144.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.330

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:

ALPK1 (HGNC:):

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=0.0021720827).

BP6

Variant 4-112432293-A-G is Benign according to our data. Variant chr4-112432293-A-G is described in ClinVar as [Benign]. Clinvar id is 2043717.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK1	NM_025144.4 linkuse as main transcript	c.2746A>G	p.Asn916Asp	missense_variant	11/16	ENST00000650871.1	NP_079420.3	Q96QP1-1
ALPK1	NM_001102406.2 linkuse as main transcript	c.2746A>G	p.Asn916Asp	missense_variant	11/16		NP_001095876.1	Q96QP1-1
ALPK1	NM_001253884.2 linkuse as main transcript	c.2512A>G	p.Asn838Asp	missense_variant	10/15		NP_001240813.1	Q96QP1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1 linkuse as main transcript	c.2746A>G	p.Asn916Asp	missense_variant	11/16		NM_025144.4	ENSP00000498374.1		Q96QP1-1

Frequencies

GnomAD3 genomes

AF:

0.00620

AC:

943

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0699

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.0414

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00845

AC:

2124

AN:

251300

Hom.:

AF XY:

0.00830

AC XY:

1127

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0613

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00371

AC:

5427

AN:

1461890

Hom.:

143

Cov.:

AF XY:

0.00368

AC XY:

2674

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.0713

Gnomad4 SAS exome

AF:

0.00255

Gnomad4 FIN exome

AF:

0.0311

Gnomad4 NFE exome

AF:

0.000291

Gnomad4 OTH exome

AF:

0.00495

GnomAD4 genome

AF:

0.00621

AC:

946

AN:

152312

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

622

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0700

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.0414

Gnomad4 NFE

AF:

0.000970

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00321

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00783

AC:

951

Asia WGS

AF:

0.0330

AC:

116

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

0.083

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.42

DANN

Benign

0.96

DEOGEN2

Benign

0.0034

.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.54

T;T;.

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

.;L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

0.060

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.47

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0070

.;B;B

Vest4

0.044

MVP

0.15

MPC

0.099

ClinPred

0.0029

GERP RS

0.32

Varity_R

0.062

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