NM_006721.4:c.878-14432G>T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADK	NM_006721.4	c.878-14432G>T		intron_variant	Intron 9 of 10	ENST00000539909.6	NP_006712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADK	ENST00000539909.6	c.878-14432G>T		intron_variant	Intron 9 of 10	2	NM_006721.4	ENSP00000443965.2

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

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.552

Gnomad4 EAS exome AF: 0.0154

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.372

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

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.0188

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.376

Alfa AF: 0.416 Hom.: 27143

Bravo AF: 0.330

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs1538311; hg19: chr10-76415509;