chr7-2250887-C-T

Variant names:

• chr7-2250887-C-T
• rs1799832
• NM_002452.4:c.357C>T

Variant summary

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

The NM_198949.2(NUDT1):​c.426C>T​(p.Asp142Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,992 control chromosomes in the GnomAD database, including 27,388 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 0.16 (2166 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25222 hom.)
• Consequence: NUDT1 NM_198949.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 21 publications found

Genes affected

NUDT1 (HGNC:8048): (nudix hydrolase 1) Misincorporation of oxidized nucleoside triphosphates into DNA/RNA during replication and transcription can cause mutations that may result in carcinogenesis or neurodegeneration. The protein encoded by this gene is an enzyme that hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy rATP, to monophosphates, thereby preventing misincorporation. The encoded protein is localized mainly in the cytoplasm, with some in the mitochondria, suggesting that it is involved in the sanitization of nucleotide pools both for nuclear and mitochondrial genomes. Several alternatively spliced transcript variants, some of which encode distinct isoforms, have been identified. Additional variants have been observed, but their full-length natures have not been determined. A rare single-nucleotide polymorphism that results in the production of an additional, longer isoform (p26) has been described. [provided by RefSeq, Dec 2018]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.139 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198949.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT1	NM_002452.4	MANE Select	c.357C>T	p.Asp119Asp	synonymous	Exon 4 of 4	NP_002443.3
	NUDT1	NM_198949.2		c.426C>T	p.Asp142Asp	synonymous	Exon 5 of 5	NP_945187.1
	NUDT1	NM_198952.2		c.426C>T	p.Asp142Asp	synonymous	Exon 5 of 5	NP_945190.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT1	ENST00000356714.6	TSL:1 MANE Select	c.357C>T	p.Asp119Asp	synonymous	Exon 4 of 4	ENSP00000349148.1
	NUDT1	ENST00000343985.8	TSL:1	c.426C>T	p.Asp142Asp	synonymous	Exon 4 of 4	ENSP00000339503.4
	NUDT1	ENST00000397048.5	TSL:1	c.426C>T	p.Asp142Asp	synonymous	Exon 5 of 5	ENSP00000380241.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24857 AN: 152104 Hom.: 2157 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.200

GnomAD2 exomes AF: 0.178 AC: 44754 AN: 251486 AF XY: 0.180

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.0592

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.182 AC: 266565 AN: 1461770 Hom.: 25222 Cov.: 37 AF XY: 0.183 AC XY: 132920 AN XY: 727192

African (AFR) AF: 0.106 AC: 3553 AN: 33480

American (AMR) AF: 0.195 AC: 8725 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6319 AN: 26134

East Asian (EAS) AF: 0.0510 AC: 2024 AN: 39696

South Asian (SAS) AF: 0.187 AC: 16156 AN: 86256

European-Finnish (FIN) AF: 0.159 AC: 8477 AN: 53406

Middle Eastern (MID) AF: 0.279 AC: 1607 AN: 5768

European-Non Finnish (NFE) AF: 0.187 AC: 208482 AN: 1111922

Other (OTH) AF: 0.186 AC: 11222 AN: 60388

GnomAD4 genome AF: 0.164 AC: 24892 AN: 152222 Hom.: 2166 Cov.: 32 AF XY: 0.163 AC XY: 12105 AN XY: 74420

African (AFR) AF: 0.109 AC: 4535 AN: 41536

American (AMR) AF: 0.212 AC: 3238 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3470

East Asian (EAS) AF: 0.0628 AC: 326 AN: 5190

South Asian (SAS) AF: 0.206 AC: 994 AN: 4828

European-Finnish (FIN) AF: 0.151 AC: 1601 AN: 10594

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12649 AN: 68008

Other (OTH) AF: 0.198 AC: 417 AN: 2110

Alfa AF: 0.183 Hom.: 5296

Bravo AF: 0.167

Asia WGS AF: 0.145 AC: 505 AN: 3478

EpiCase AF: 0.193

EpiControl AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.49
DANN	Benign	0.62
PhyloP100		-0.14
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1799832; hg19: chr7-2290522; COSMIC: COSV56128992; COSMIC: COSV56128992;