10-74655751-G-T

Variant names:

• chr10-74655751-G-T
• rs1538311
• NM_006721.4:c.878-14432G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006721.4(ADK):​c.878-14432G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 484,096 control chromosomes in the GnomAD database, including 33,484 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 0.34 (9918 hom., cov: 29)
  • Exomes 𝑓: 0.35 (23566 hom.)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 8 publications found

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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51533 AN: 151418 Hom.: 9917 Cov.: 29

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.352 AC: 117040 AN: 332560 Hom.: 23566 Cov.: 0 AF XY: 0.346 AC XY: 64128 AN XY: 185102

African (AFR) AF: 0.206 AC: 1942 AN: 9442

American (AMR) AF: 0.212 AC: 5059 AN: 23904

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 4628 AN: 8386

East Asian (EAS) AF: 0.0154 AC: 223 AN: 14472

South Asian (SAS) AF: 0.215 AC: 11149 AN: 51950

European-Finnish (FIN) AF: 0.367 AC: 10370 AN: 28250

Middle Eastern (MID) AF: 0.423 AC: 871 AN: 2060

European-Non Finnish (NFE) AF: 0.432 AC: 76752 AN: 177826

Other (OTH) AF: 0.372 AC: 6046 AN: 16270

GnomAD4 genome AF: 0.340 AC: 51534 AN: 151536 Hom.: 9918 Cov.: 29 AF XY: 0.332 AC XY: 24592 AN XY: 73988

African (AFR) AF: 0.218 AC: 8996 AN: 41310

American (AMR) AF: 0.302 AC: 4600 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1991 AN: 3460

East Asian (EAS) AF: 0.0188 AC: 97 AN: 5166

South Asian (SAS) AF: 0.204 AC: 976 AN: 4788

European-Finnish (FIN) AF: 0.364 AC: 3798 AN: 10440

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.439 AC: 29796 AN: 67832

Other (OTH) AF: 0.376 AC: 792 AN: 2108

Alfa AF: 0.402 Hom.: 39489

Bravo AF: 0.330

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.53
PhyloP100		-0.17
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1538311; hg19: chr10-76415509;