rs6686

Variant names:

• chr10-12167753-T-C
• rs6686
• NM_014142.4:c.609A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-12167753-T-C
• chr10-12167753-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014142.4(NUDT5):​c.609A>G​(p.Ala203Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,613,664 control chromosomes in the GnomAD database, including 199,625 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 0.47 (17235 hom., cov: 32)
  • Exomes 𝑓: 0.50 (182390 hom.)
• Consequence: NUDT5 NM_014142.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.91

Genes affected

NUDT5 (HGNC:8052): (nudix hydrolase 5) This gene belongs to the Nudix (nucleoside diphosphate linked moiety X) hydrolase superfamily. The encoded enzyme catalyzes the hydrolysis of modified nucleoside diphosphates, including ADP-ribose (ADPR) and 8-oxoGua-containing 8-oxo-dADP and 8-oxo-dGDP. Protein-bound ADP ribose can be hazardous to the cell because it can modify some amino acid residues, resulting in the inhibition of ATP-activated potassium channels. 8-oxoGua is an oxidized form of guanine that can potentially alter genetic information by pairing with adenine and cytosine in RNA. Presence of 8-oxoGua in RNA results in formation of abnormal proteins due to translational errors. [provided by RefSeq, Aug 2013]

SEC61A2 (HGNC:17702): (SEC61 translocon subunit alpha 2) The protein encoded by this gene has similarity to a mouse protein which suggests a role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. It may also be required for the assembly of membrane and secretory proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP7: Synonymous conserved (PhyloP=-4.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT5	NM_014142.4	c.609A>G	p.Ala203Ala	synonymous_variant	Exon 10 of 10	ENST00000491614.6	NP_054861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT5	ENST00000491614.6	c.609A>G	p.Ala203Ala	synonymous_variant	Exon 10 of 10	1	NM_014142.4	ENSP00000419628.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72034 AN: 151968 Hom.: 17230 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.445

GnomAD2 exomes AF: 0.479 AC: 120251 AN: 251250 AF XY: 0.470

Gnomad AFR exome AF: 0.444

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.446

Gnomad EAS exome AF: 0.559

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.503

Gnomad OTH exome AF: 0.476

GnomAD4 exome AF: 0.497 AC: 726141 AN: 1461578 Hom.: 182390 Cov.: 56 AF XY: 0.493 AC XY: 358143 AN XY: 727088

Gnomad4 AFR exome AF: 0.441 AC: 14744 AN: 33468

Gnomad4 AMR exome AF: 0.509 AC: 22761 AN: 44678

Gnomad4 ASJ exome AF: 0.448 AC: 11691 AN: 26122

Gnomad4 EAS exome AF: 0.546 AC: 21684 AN: 39684

Gnomad4 SAS exome AF: 0.362 AC: 31212 AN: 86228

Gnomad4 FIN exome AF: 0.436 AC: 23274 AN: 53388

Gnomad4 NFE exome AF: 0.512 AC: 569368 AN: 1111854

Gnomad4 Remaining exome AF: 0.482 AC: 29132 AN: 60390

GnomAD4 genome AF: 0.474 AC: 72058 AN: 152086 Hom.: 17235 Cov.: 32 AF XY: 0.466 AC XY: 34651 AN XY: 74340

Gnomad4 AFR AF: 0.447 AC: 0.447418 AN: 0.447418

Gnomad4 AMR AF: 0.443 AC: 0.442648 AN: 0.442648

Gnomad4 ASJ AF: 0.451 AC: 0.451009 AN: 0.451009

Gnomad4 EAS AF: 0.554 AC: 0.554028 AN: 0.554028

Gnomad4 SAS AF: 0.367 AC: 0.367262 AN: 0.367262

Gnomad4 FIN AF: 0.439 AC: 0.438635 AN: 0.438635

Gnomad4 NFE AF: 0.508 AC: 0.507942 AN: 0.507942

Gnomad4 OTH AF: 0.439 AC: 0.439451 AN: 0.439451

Alfa AF: 0.489 Hom.: 17597

Bravo AF: 0.478

Asia WGS AF: 0.403 AC: 1405 AN: 3478

EpiCase AF: 0.488

EpiControl AF: 0.483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.23
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Publications

LitVar

Other links and lift over

dbSNP: rs6686; hg19: chr10-12209752; COSMIC: COSV53651031; COSMIC: COSV53651031;