dbSNP rs1336472: AK4:c.*4070G>A (chr1-65230247-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013410.4(AK4):c.*4070G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,014 control chromosomes in the GnomAD database, including 27,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 27615 hom., cov: 32)

Exomes 𝑓: 0.50 ( 3 hom. )

Consequence

AK4
NM_013410.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Publications

11 publications found

Variant links:

Genes affected

AK4 (HGNC:363): (adenylate kinase 4) This gene encodes a member of the adenylate kinase family of enzymes. The encoded protein is localized to the mitochondrial matrix. Adenylate kinases regulate the adenine and guanine nucleotide compositions within a cell by catalyzing the reversible transfer of phosphate group among these nucleotides. Five isozymes of adenylate kinase have been identified in vertebrates. Expression of these isozymes is tissue-specific and developmentally regulated. A pseudogene for this gene has been located on chromosome 17. Three transcript variants encoding the same protein have been identified for this gene. Sequence alignment suggests that the gene defined by NM_013410, NM_203464, and NM_001005353 is located on chromosome 1. [provided by RefSeq, Jul 2008]

AK4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK4	NM_013410.4 link	c.*4070G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000327299.8	NP_037542.1	P27144

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AK4	ENST00000327299.8 link	c.*4070G>A	3_prime_UTR_variant	Exon 5 of 5	1	NM_013410.4	ENSP00000322175.7	P27144
AK4	ENST00000395334.6 link	c.*4070G>A	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000378743.2	P27144
AK4	ENST00000545314.5 link	c.*4070G>A	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000445912.1	P27144

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85074

AN:

151872

Hom.:

27550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.889

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.587

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.528

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.450

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.561

AC:

85208

AN:

151992

Hom.:

27615

Cov.:

AF XY:

0.561

AC XY:

41679

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.889

AC:

36897

AN:

41486

American (AMR)

AF:

0.588

AC:

8971

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

1345

AN:

3468

East Asian (EAS)

AF:

0.672

AC:

3457

AN:

5144

South Asian (SAS)

AF:

0.513

AC:

2468

AN:

4810

European-Finnish (FIN)

AF:

0.358

AC:

3771

AN:

10546

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.392

AC:

26640

AN:

67962

Other (OTH)

AF:

0.535

AC:

1129

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1545

3090

4636

6181

7726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.467

Hom.:

47355

Bravo

AF:

0.592

Asia WGS

AF:

0.641

AC:

2231

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.29

(source)

DANN

Benign

0.48

PhyloP100

-1.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over