rs2369679

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152327.5(AK7):c.1167C>G(p.Asn389Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 1,613,062 control chromosomes in the GnomAD database, including 557,097 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N389D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.86 ( 56919 hom., cov: 31)

Exomes 𝑓: 0.83 ( 500178 hom. )

Consequence

AK7
NM_152327.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00100

Publications

34 publications found

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:

RPL23AP10 (HGNC:19804): (ribosomal protein L23a pseudogene 10)

RPL23AP10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=7.4447956E-7).

BP6

Variant 14-96456415-C-G is Benign according to our data. Variant chr14-96456415-C-G is described in ClinVar as Benign. ClinVar VariationId is 402363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152327.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AK7	NM_152327.5	MANE Select	c.1167C>G	p.Asn389Lys	missense	Exon 11 of 18	NP_689540.2
AK7	NM_001350888.2		c.1167C>G	p.Asn389Lys	missense	Exon 11 of 17	NP_001337817.1
AK7	NM_001350890.2		c.1167C>G	p.Asn389Lys	missense	Exon 11 of 17	NP_001337819.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AK7	ENST00000267584.9	TSL:1 MANE Select	c.1167C>G	p.Asn389Lys	missense	Exon 11 of 18	ENSP00000267584.4
AK7	ENST00000856706.1		c.1251C>G	p.Asn417Lys	missense	Exon 12 of 19	ENSP00000526765.1
AK7	ENST00000856705.1		c.1167C>G	p.Asn389Lys	missense	Exon 11 of 17	ENSP00000526764.1

Frequencies

GnomAD3 genomes

AF:

0.863

AC:

131133

AN:

152010

Hom.:

56866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.952

Gnomad AMI

AF:

0.860

Gnomad AMR

AF:

0.832

Gnomad ASJ

AF:

0.903

Gnomad EAS

AF:

0.956

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.826

Gnomad OTH

AF:

0.889

GnomAD2 exomes

AF:

0.834

AC:

209413

AN:

251080

AF XY:

0.832

show subpopulations

Gnomad AFR exome

AF:

0.953

Gnomad AMR exome

AF:

0.774

Gnomad ASJ exome

AF:

0.903

Gnomad EAS exome

AF:

0.962

Gnomad FIN exome

AF:

0.760

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.826

AC:

1207270

AN:

1460934

Hom.:

500178

Cov.:

AF XY:

0.826

AC XY:

600480

AN XY:

726752

show subpopulations

African (AFR)

AF:

0.956

AC:

31992

AN:

33472

American (AMR)

AF:

0.782

AC:

34915

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.906

AC:

23638

AN:

26102

East Asian (EAS)

AF:

0.959

AC:

38062

AN:

39684

South Asian (SAS)

AF:

0.803

AC:

69119

AN:

86096

European-Finnish (FIN)

AF:

0.767

AC:

40895

AN:

53334

Middle Eastern (MID)

AF:

0.915

AC:

5276

AN:

5764

European-Non Finnish (NFE)

AF:

0.821

AC:

912097

AN:

1111500

Other (OTH)

AF:

0.849

AC:

51276

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

9822

19644

29467

39289

49111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20950

41900

62850

83800

104750

<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:

0.863

AC:

131245

AN:

152128

Hom.:

56919

Cov.:

AF XY:

0.859

AC XY:

63840

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.952

AC:

39526

AN:

41528

American (AMR)

AF:

0.832

AC:

12714

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.903

AC:

3135

AN:

3470

East Asian (EAS)

AF:

0.957

AC:

4953

AN:

5178

South Asian (SAS)

AF:

0.805

AC:

3886

AN:

4826

European-Finnish (FIN)

AF:

0.755

AC:

7948

AN:

10534

Middle Eastern (MID)

AF:

0.929

AC:

273

AN:

294

European-Non Finnish (NFE)

AF:

0.826

AC:

56148

AN:

68000

Other (OTH)

AF:

0.890

AC:

1878

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

891

1781

2672

3562

4453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.841

Hom.:

40757

Bravo

AF:

0.872

TwinsUK

AF:

0.823

AC:

3052

ALSPAC

AF:

0.827

AC:

3188

ESP6500AA

AF:

0.947

AC:

4171

ESP6500EA

AF:

0.832

AC:

7152

ExAC

AF:

0.838

AC:

101786

Asia WGS

AF:

0.879

AC:

3057

AN:

3478

EpiCase

AF:

0.836

EpiControl

AF:

0.844

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.25

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.040

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.10

MetaRNN

Benign

7.4e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

PhyloP100

-0.0010

PrimateAI

Benign

0.38

PROVEAN

Benign

2.5

REVEL

Benign

0.067

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.075

MutPred

0.15

Loss of ubiquitination at K385 (P = 0.0331)

MPC

0.21

ClinPred

0.00083

GERP RS

-0.45

Varity_R

0.034

gMVP

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over