Genetic Variant AK7:p.Glu53_Glu56del (chr14-96398118-CAGAGGAAGAGGA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_152327.5(AK7):c.159_170delGGAAGAGGAAGA(p.Glu53_Glu56del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000531 in 1,614,100 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 1 hom. )

Consequence

AK7
NM_152327.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.85

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_152327.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK7	NM_152327.5 link	c.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 of 18	ENST00000267584.9	NP_689540.2	Q96M32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AK7	ENST00000267584.9 link	c.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 of 18	1	NM_152327.5	ENSP00000267584.4	Q96M32
AK7	ENST00000555570.1 link	c.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 of 2	2		ENSP00000451068.1	G3V365
AK7	ENST00000556643.1 link	n.170_181delGGAAGAGGAAGA		non_coding_transcript_exon_variant	Exon 2 of 3	2
AK7	ENST00000554313.1 link	n.-79_-68delAGAGGAAGAGGA		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000374

AC:

AN:

251412

AF XY:

0.000390

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000553

AC:

808

AN:

1461828

Hom.:

AF XY:

0.000532

AC XY:

387

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

AC:

AN:

33478

Gnomad4 AMR exome

AF:

0.000358

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000232

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53374

Gnomad4 NFE exome

AF:

0.000671

AC:

746

AN:

1111998

Gnomad4 Remaining exome

AF:

0.000563

AC:

AN:

60392

Heterozygous variant carriers

108

161

215

269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000322

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000722

AC:

0.0000721883

AN:

0.0000721883

Gnomad4 AMR

AF:

0.000262

AC:

0.000261643

AN:

0.000261643

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000588

AC:

0.000588045

AN:

0.000588045

Gnomad4 OTH

AF:

0.000945

AC:

0.00094518

AN:

0.00094518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000509

Hom.:

Bravo

AF:

0.000378

EpiCase

AF:

0.000436

EpiControl

AF:

0.000652

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant, c.159_170del, results in the deletion of 4 amino acid(s) of the AK7 protein (p.Glu53_Glu56del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs776901819, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with AK7-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=126/74

polymorphism

Splicing

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