Genetic Variant NM_152572.3:c.1057C>A (chr9-132792698-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152572.3(AK8):c.1057C>A(p.His353Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. H353Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

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: 2.75

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK8	NM_152572.3 link	c.1057C>A	p.His353Asn	missense_variant	Exon 11 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.1057C>A	p.His353Asn	missense_variant	Exon 11 of 13	1	NM_152572.3	ENSP00000298545.3	Q96MA6-1
AK8	ENST00000476719.1 link	n.1494C>A		non_coding_transcript_exon_variant	Exon 10 of 12	5
AK8	ENST00000477396.5 link	n.1972C>A		non_coding_transcript_exon_variant	Exon 13 of 15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1404342

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693228

African (AFR)

AF:

0.00

AC:

AN:

31960

American (AMR)

AF:

0.00

AC:

AN:

36586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25230

East Asian (EAS)

AF:

0.00

AC:

AN:

36334

South Asian (SAS)

AF:

0.00

AC:

AN:

79446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4414

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082504

Other (OTH)

AF:

0.00

AC:

AN:

58124

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

Uncertain

0.36

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.023

Eigen_PC

Benign

-0.00012

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.4

PhyloP100

2.7

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.41

Sift

Uncertain

0.018

Sift4G

Benign

0.14

Polyphen

0.42

Vest4

0.62

MutPred

0.64

Loss of ubiquitination at K348 (P = 0.1037);

MVP

0.70

MPC

0.51

ClinPred

0.97

GERP RS

4.3

Varity_R

0.25

gMVP

0.55

Mutation Taster

=96/4

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