Genetic Variant AK7:c.948+12C>T (chr14-96449891-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_152327.5(AK7):c.948+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,464,326 control chromosomes in the GnomAD database, including 96,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 8554 hom., cov: 30)

Exomes 𝑓: 0.35 ( 87676 hom. )

Consequence

AK7
NM_152327.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.76

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 14-96449891-C-T is Benign according to our data. Variant chr14-96449891-C-T is described in ClinVar as [Benign]. Clinvar id is 402361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK7	NM_152327.5 link	c.948+12C>T		intron_variant	Intron 9 of 17	ENST00000267584.9	NP_689540.2	Q96M32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK7	ENST00000267584.9 link	c.948+12C>T		intron_variant	Intron 9 of 17	1	NM_152327.5	ENSP00000267584.4		Q96M32

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

49689

AN:

113812

Hom.:

8559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.521

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.476

GnomAD3 exomes

AF:

0.393

AC:

72893

AN:

185608

Hom.:

13450

AF XY:

0.396

AC XY:

40105

AN XY:

101204

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.423

Gnomad ASJ exome

AF:

0.464

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.412

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.354

AC:

478176

AN:

1350472

Hom.:

87676

Cov.:

AF XY:

0.357

AC XY:

240842

AN XY:

674194

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.359

Gnomad4 OTH exome

AF:

0.363

GnomAD4 genome

AF:

0.436

AC:

49681

AN:

113854

Hom.:

8554

Cov.:

AF XY:

0.435

AC XY:

24165

AN XY:

55516

show subpopulations

Gnomad4 AFR

AF:

0.442

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.494

Gnomad4 EAS

AF:

0.342

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.436

Gnomad4 OTH

AF:

0.472

Alfa

AF:

0.366

Hom.:

15524

Bravo

AF:

0.328

Asia WGS

AF:

0.274

AC:

944

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.028

DANN

Benign

0.51

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