14-96449891-C-T

Variant names:

• chr14-96449891-C-T
• rs10444759
• NM_152327.5:c.948+12C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.76

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]

ACMG classification

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	c.948+12C>T		intron_variant	Intron 9 of 17	ENST00000267584.9	NP_689540.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.437 AC: 49689 AN: 113812 Hom.: 8559 Cov.: 30

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

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.: 25 AF XY: 0.357 AC XY: 240842 AN XY: 674194

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.: 30 AF XY: 0.435 AC XY: 24165 AN XY: 55516

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

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

Other links and lift over

dbSNP: rs10444759; hg19: chr14-96916228;