dbSNP rs200678908: AK8:p.Gly469Val (chr9-132725722-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152572.3(AK8):c.1406G>T(p.Gly469Val) 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. 15/22 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. G469E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AK8
NM_152572.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.07

Publications

2 publications found

Variant links:

Genes affected

AK8 (HGNC:26526): (adenylate kinase 8) Enables AMP binding activity and nucleobase-containing compound kinase activity. Involved in nucleoside diphosphate phosphorylation and nucleoside triphosphate biosynthetic process. Located in 9+2 motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

AK8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30710733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK8	NM_152572.3 link	c.1406G>T	p.Gly469Val	missense_variant	Exon 13 of 13	ENST00000298545.4	NP_689785.1	Q96MA6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AK8	ENST00000298545.4 link	c.1406G>T	p.Gly469Val	missense_variant	Exon 13 of 13	1	NM_152572.3	ENSP00000298545.3	Q96MA6-1
AK8	ENST00000467161.1 link	n.349G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
AK8	ENST00000476719.1 link	n.1843G>T		non_coding_transcript_exon_variant	Exon 12 of 12	5
AK8	ENST00000477396.5 link	n.2321G>T		non_coding_transcript_exon_variant	Exon 15 of 15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

209106

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1430360

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707108

African (AFR)

AF:

0.00

AC:

AN:

33248

American (AMR)

AF:

0.00

AC:

AN:

39388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25464

East Asian (EAS)

AF:

0.00

AC:

AN:

38838

South Asian (SAS)

AF:

0.00

AC:

AN:

81836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094752

Other (OTH)

AF:

0.00

AC:

AN:

59300

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.052

Eigen

Benign

-0.059

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.061

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.7

PhyloP100

3.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

REVEL

Benign

0.25

Sift

Benign

0.50

Sift4G

Benign

0.50

Polyphen

0.43

Vest4

0.42

MutPred

0.47

Loss of glycosylation at S468 (P = 0.0384);

MVP

0.66

MPC

0.58

ClinPred

0.72

GERP RS

5.1

Varity_R

0.16

gMVP

0.60

Mutation Taster

=82/18

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over