rs2074380

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G870V) has been classified as Uncertain significance.

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

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ALPK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ALPK1	NM_025144.4 link	c.2608G>A	p.Gly870Ser	missense_variant	Exon 11 of 16	ENST00000650871.1	NP_079420.3	Q96QP1-1
ALPK1	NM_001102406.2 link	c.2608G>A	p.Gly870Ser	missense_variant	Exon 11 of 16		NP_001095876.1	Q96QP1-1
ALPK1	NM_001253884.2 link	c.2374G>A	p.Gly792Ser	missense_variant	Exon 10 of 15		NP_001240813.1	Q96QP1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1 link	c.2608G>A	p.Gly870Ser	missense_variant	Exon 11 of 16		NM_025144.4	ENSP00000498374.1		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

GnomAD2 exomes

AF:

0.00851

AC:

2137

AN:

251122

AF XY:

0.00836

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 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

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000291

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00237

AC:

AN:

26136

East Asian (EAS)

AF:

0.0756

AC:

3002

AN:

39698

South Asian (SAS)

AF:

0.00255

AC:

220

AN:

86258

European-Finnish (FIN)

AF:

0.0311

AC:

1659

AN:

53420

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000305

AC:

339

AN:

1112010

Other (OTH)

AF:

0.00500

AC:

302

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

391

783

1174

1566

1957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00623

AC:

949

AN:

152298

Hom.:

Cov.:

AF XY:

0.00837

AC XY:

623

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41568

American (AMR)

AF:

0.000327

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.0712

AC:

369

AN:

5184

South Asian (SAS)

AF:

0.00685

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0414

AC:

440

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000985

AC:

AN:

68016

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

152

203

254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00225

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

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

1.2

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over