Genetic Variant NM_006721.4:c.878-14432G>A (chr10-74655751-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006721.4(ADK):c.878-14432G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,516 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADK
NM_006721.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.174

Publications

8 publications found

Variant links:

Genes affected

ADK (HGNC:257): (adenosine kinase) This gene an enzyme which catalyzes the transfer of the gamma-phosphate from ATP to adenosine, thereby serving as a regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of the enzyme could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as anti-inflammatory agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ADK links:

POLR3DP1 (HGNC:45107): (RNA polymerase III subunit D pseudogene 1)

POLR3DP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006721.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADK	NM_006721.4	MANE Select	c.878-14432G>A	intron	N/A	NP_006712.2
ADK	NM_001123.4		c.827-14432G>A	intron	N/A	NP_001114.2
ADK	NM_001202449.2		c.773-14432G>A	intron	N/A	NP_001189378.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADK	ENST00000539909.6	TSL:2 MANE Select	c.878-14432G>A	intron	N/A	ENSP00000443965.2
ADK	ENST00000286621.7	TSL:1	c.878-14432G>A	intron	N/A	ENSP00000286621.3
ADK	ENST00000372734.5	TSL:1	c.827-14432G>A	intron	N/A	ENSP00000361819.3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

333704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

185756

African (AFR)

AF:

0.00

AC:

AN:

9466

American (AMR)

AF:

0.00

AC:

AN:

24002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8438

East Asian (EAS)

AF:

0.00

AC:

AN:

14476

South Asian (SAS)

AF:

0.00

AC:

AN:

52072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2072

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

178470

Other (OTH)

AF:

0.00

AC:

AN:

16322

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41212

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67888

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

39489

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.2

(source)

DANN

Benign

0.51

PhyloP100

-0.17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over