rs2275554

Variant names:

• chr14-96404767-G-A
• rs2275554
• NM_152327.5:c.305G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152327.5(AK7):​c.305G>A​(p.Arg102Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,597,578 control chromosomes in the GnomAD database, including 46,816 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4097 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42719 hom.)
• Consequence: AK7 NM_152327.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.47
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• primary ciliary dyskinesia

  Inheritance: AR Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen
• spermatogenic failure 27

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016051829).
• BP6: Variant 14-96404767-G-A is Benign according to our data. Variant chr14-96404767-G-A is described in ClinVar as Benign. ClinVar VariationId is 402360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK7	NM_152327.5	c.305G>A	p.Arg102Gln	missense_variant	Exon 3 of 18	ENST00000267584.9	NP_689540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK7	ENST00000267584.9	c.305G>A	p.Arg102Gln	missense_variant	Exon 3 of 18	1	NM_152327.5	ENSP00000267584.4
AK7	ENST00000554313.1	n.77G>A		non_coding_transcript_exon_variant	Exon 2 of 5	3
AK7	ENST00000556643.1	n.316G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35017 AN: 151846 Hom.: 4097 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.234

GnomAD2 exomes AF: 0.219 AC: 55020 AN: 251018 AF XY: 0.221

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.187

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.240 AC: 346720 AN: 1445612 Hom.: 42719 Cov.: 30 AF XY: 0.238 AC XY: 170960 AN XY: 717060

African (AFR) AF: 0.211 AC: 7030 AN: 33254

American (AMR) AF: 0.170 AC: 7548 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8401 AN: 25928

East Asian (EAS) AF: 0.201 AC: 7912 AN: 39350

South Asian (SAS) AF: 0.178 AC: 15223 AN: 85530

European-Finnish (FIN) AF: 0.198 AC: 10509 AN: 53056

Middle Eastern (MID) AF: 0.201 AC: 1146 AN: 5712

European-Non Finnish (NFE) AF: 0.250 AC: 274519 AN: 1098668

Other (OTH) AF: 0.242 AC: 14432 AN: 59590

GnomAD4 genome AF: 0.231 AC: 35039 AN: 151966 Hom.: 4097 Cov.: 32 AF XY: 0.227 AC XY: 16844 AN XY: 74264

African (AFR) AF: 0.223 AC: 9253 AN: 41442

American (AMR) AF: 0.204 AC: 3115 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1002 AN: 5158

South Asian (SAS) AF: 0.174 AC: 839 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2054 AN: 10554

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16833 AN: 67946

Other (OTH) AF: 0.237 AC: 500 AN: 2112

Alfa AF: 0.246 Hom.: 12129

Bravo AF: 0.232

TwinsUK AF: 0.239 AC: 885

ALSPAC AF: 0.252 AC: 972

ESP6500AA AF: 0.229 AC: 1009

ESP6500EA AF: 0.255 AC: 2191

ExAC AF: 0.218 AC: 26487

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	0.090
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.026
Sift	Benign	0.15	T
Sift4G	Benign	0.16	T
Polyphen		0.15	B
Vest4		0.055
MPC		0.23
ClinPred		0.010	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2275554; hg19: chr14-96871104; COSMIC: COSV50871708;