Variant 9-127868063-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_000476.3(AK1):c.530G>T(p.Gly177Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AK1
NM_000476.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

Genes affected

AK1 (HGNC:361): (adenylate kinase 1) This gene encodes an adenylate kinase enzyme involved in energy metabolism and homeostasis of cellular adenine nucleotide ratios in different intracellular compartments. This gene is highly expressed in skeletal muscle, brain and erythrocytes. Certain mutations in this gene resulting in a functionally inadequate enzyme are associated with a rare genetic disorder causing nonspherocytic hemolytic anemia. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene shares readthrough transcripts with the upstream ST6GALNAC6 gene. [provided by RefSeq, Jan 2022]

AK1 links:

ENSG00000257524 (HGNC:):

ENSG00000257524 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity KAD1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK1	NM_000476.3 linkuse as main transcript	c.530G>T	p.Gly177Val	missense_variant	7/7	ENST00000644144.2	NP_000467.1	P00568Q6FGX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK1	ENST00000644144.2 linkuse as main transcript	c.530G>T	p.Gly177Val	missense_variant	7/7	NM_000476.3	ENSP00000494600.1	P00568
ENSG00000257524	ENST00000646171.1 linkuse as main transcript	n.*563G>T		non_coding_transcript_exon_variant	13/13		ENSP00000495484.1	A0A2R8YFX0
ENSG00000257524	ENST00000646171.1 linkuse as main transcript	n.*563G>T		3_prime_UTR_variant	13/13		ENSP00000495484.1	A0A2R8YFX0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249166

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hemolytic anemia due to adenylate kinase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

May 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

D;D;D;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

.;.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.62

D;D;D;D

MetaSVM

Uncertain

-0.0060

MutationAssessor

Pathogenic

3.0

M;M;M;.

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.7

D;.;D;D

REVEL

Uncertain

0.47

Sift

Benign

0.045

D;.;D;D

Sift4G

Benign

0.18

T;.;T;T

Polyphen

0.91

P;P;P;.

Vest4

0.40

MutPred

0.44

Loss of disorder (P = 0.0433);Loss of disorder (P = 0.0433);Loss of disorder (P = 0.0433);.;

MVP

0.47

MPC

0.93

ClinPred

0.98

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.72

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