dbSNP rs116298211: AK7:p.Leu673Pro (chr14-96486941-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152327.5(AK7):c.2018T>C(p.Leu673Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00227 in 1,614,046 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

AK7
NM_152327.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1B:1

Conservation

PhyloP100: 6.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08193272).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK7	NM_152327.5 link	c.2018T>C	p.Leu673Pro	missense_variant	Exon 17 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.2018T>C	p.Leu673Pro	missense_variant	Exon 17 of 18	1	NM_152327.5	ENSP00000267584.4		Q96M32
AK7	ENST00000554706.1 link	c.281T>C	p.Leu94Pro	missense_variant	Exon 2 of 3	3		ENSP00000450453.1		H0YIY5

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00146

AC:

368

AN:

251406

Hom.:

AF XY:

0.00152

AC XY:

206

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00259

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00236

AC:

3451

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

1657

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00291

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152304

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00201

Hom.:

Bravo

AF:

0.00138

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00167

AC:

203

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00190

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Spermatogenic failure 27

Pathogenic:1

Oct 15, 2018

SIB Swiss Institute of Bioinformatics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

This variant is interpreted as Likely Pathogenic, for Spermatogenic failure 27, autosomal recessive. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect (https://www.ncbi.nlm.nih.gov/pubmed/29365104). PM1-Supporting => PM1 downgraded in strength to Supporting (https://www.uniprot.org/uniprot/Q96M32). PM2-Supporting => PM2 downgraded in strength to Supporting. -

not provided

Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.082

MetaSVM

Uncertain

0.037

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.77

MVP

0.83

MPC

0.96

ClinPred

0.090

GERP RS

5.5

Varity_R

0.92

gMVP

0.86

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