rs2369679

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152327.5(AK7):c.1167C>G(p.Asn389Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 1,613,062 control chromosomes in the GnomAD database, including 557,097 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.86 ( 56919 hom., cov: 31)

Exomes 𝑓: 0.83 ( 500178 hom. )

Consequence

AK7
NM_152327.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00100

Variant links:

Genes affected

AK7 (HGNC:20091): (adenylate kinase 7) This gene encodes a member of the adenylate kinase family of enzymes. The encoded enzyme is a phosphotransferase that catalyzes the reversible phosphorylation of adenine nucleotides. This enzyme plays a role in energy homeostasis of the cell. Alternative splicing results in multiple transcript variants. Mutations in the mouse gene are associated with primary ciliary dyskinesia. [provided by RefSeq, Apr 2017]

AK7 links:

RPL23AP10 (HGNC:19804): (ribosomal protein L23a pseudogene 10)

RPL23AP10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.4447956E-7).

BP6

Variant 14-96456415-C-G is Benign according to our data. Variant chr14-96456415-C-G is described in ClinVar as [Benign]. Clinvar id is 402363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK7	NM_152327.5 link	c.1167C>G	p.Asn389Lys	missense_variant	Exon 11 of 18	ENST00000267584.9	NP_689540.2	Q96M32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK7	ENST00000267584.9 link	c.1167C>G	p.Asn389Lys	missense_variant	Exon 11 of 18	1	NM_152327.5	ENSP00000267584.4		Q96M32
RPL23AP10	ENST00000489946.1 link	n.*161G>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.863

AC:

131133

AN:

152010

Hom.:

56866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.952

Gnomad AMI

AF:

0.860

Gnomad AMR

AF:

0.832

Gnomad ASJ

AF:

0.903

Gnomad EAS

AF:

0.956

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.826

Gnomad OTH

AF:

0.889

GnomAD3 exomes

AF:

0.834

AC:

209413

AN:

251080

Hom.:

87949

AF XY:

0.832

AC XY:

112908

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.953

Gnomad AMR exome

AF:

0.774

Gnomad ASJ exome

AF:

0.903

Gnomad EAS exome

AF:

0.962

Gnomad SAS exome

AF:

0.804

Gnomad FIN exome

AF:

0.760

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.826

AC:

1207270

AN:

1460934

Hom.:

500178

Cov.:

AF XY:

0.826

AC XY:

600480

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.956

Gnomad4 AMR exome

AF:

0.782

Gnomad4 ASJ exome

AF:

0.906

Gnomad4 EAS exome

AF:

0.959

Gnomad4 SAS exome

AF:

0.803

Gnomad4 FIN exome

AF:

0.767

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.849

GnomAD4 genome

AF:

0.863

AC:

131245

AN:

152128

Hom.:

56919

Cov.:

AF XY:

0.859

AC XY:

63840

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.952

Gnomad4 AMR

AF:

0.832

Gnomad4 ASJ

AF:

0.903

Gnomad4 EAS

AF:

0.957

Gnomad4 SAS

AF:

0.805

Gnomad4 FIN

AF:

0.755

Gnomad4 NFE

AF:

0.826

Gnomad4 OTH

AF:

0.890

Alfa

AF:

0.841

Hom.:

40757

Bravo

AF:

0.872

TwinsUK

AF:

0.823

AC:

3052

ALSPAC

AF:

0.827

AC:

3188

ESP6500AA

AF:

0.947

AC:

4171

ESP6500EA

AF:

0.832

AC:

7152

ExAC

AF:

0.838

AC:

101786

Asia WGS

AF:

0.879

AC:

3057

AN:

3478

EpiCase

AF:

0.836

EpiControl

AF:

0.844

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.25

DANN

Benign

0.54

DEOGEN2

Benign

0.040

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.10

MetaRNN

Benign

7.4e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

PrimateAI

Benign

0.38

PROVEAN

Benign

2.5

REVEL

Benign

0.067

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.075

MutPred

0.15

Loss of ubiquitination at K385 (P = 0.0331);

MPC

0.21

ClinPred

0.00083

GERP RS

-0.45

Varity_R

0.034

gMVP

0.23

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