rs6686

Positions:

• chr10-12167753-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014142.4(NUDT5):​c.609A>G​(p.Ala203=) 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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NUDT5	NM_014142.4	c.609A>G	p.Ala203=	synonymous_variant	10/10	ENST00000491614.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT5	ENST00000491614.6	c.609A>G	p.Ala203=	synonymous_variant	10/10	1	NM_014142.4	P1

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

GnomAD3 exomes AF: 0.479 AC: 120251 AN: 251250 Hom.: 29354 AF XY: 0.470 AC XY: 63832 AN XY: 135800

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 SAS exome AF: 0.360

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

Gnomad4 AMR exome AF: 0.509

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.512

Gnomad4 OTH exome AF: 0.482

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

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.439

Alfa AF: 0.489 Hom.: 15150

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

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;