7-2251764-G-A

Variant names:

• chr7-2251764-G-A
• rs2270052
• ENST00000862416.1:c.*763G>A

Variant summary

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

The ENST00000862416.1(NUDT1):​c.*763G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,778 control chromosomes in the GnomAD database, including 7,992 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 0.30 (7951 hom., cov: 33)
  • Exomes 𝑓: 0.33 (41 hom.)
• Consequence: NUDT1 ENST00000862416.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 9 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]

SNX8 (HGNC:14972): (sorting nexin 8) Enables identical protein binding activity and phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000862416.1. 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
	SNX8	NM_013321.4	MANE Select	c.*3292C>T		downstream_gene	N/A	NP_037453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT1	ENST00000862416.1		c.*763G>A		3_prime_UTR	Exon 5 of 5	ENSP00000532475.1
	NUDT1	ENST00000862417.1		c.*763G>A		3_prime_UTR	Exon 5 of 5	ENSP00000532476.1
	SNX8	ENST00000222990.8	TSL:1 MANE Select	c.*3292C>T		downstream_gene	N/A	ENSP00000222990.3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44934 AN: 152058 Hom.: 7945 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.331 AC: 199 AN: 602 Hom.: 41 Cov.: 0 AF XY: 0.328 AC XY: 103 AN XY: 314

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.284 AC: 21 AN: 74

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.278 AC: 5 AN: 18

European-Finnish (FIN) AF: 0.167 AC: 2 AN: 12

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.351 AC: 168 AN: 478

Other (OTH) AF: 0.200 AC: 2 AN: 10

GnomAD4 genome AF: 0.295 AC: 44961 AN: 152176 Hom.: 7951 Cov.: 33 AF XY: 0.299 AC XY: 22201 AN XY: 74366

African (AFR) AF: 0.105 AC: 4370 AN: 41540

American (AMR) AF: 0.363 AC: 5550 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2890 AN: 5172

South Asian (SAS) AF: 0.308 AC: 1488 AN: 4824

European-Finnish (FIN) AF: 0.322 AC: 3405 AN: 10562

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25211 AN: 68000

Other (OTH) AF: 0.314 AC: 663 AN: 2112

Alfa AF: 0.297 Hom.: 1667

Bravo AF: 0.293

Asia WGS AF: 0.447 AC: 1552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.013
DANN	Benign	0.78
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2270052; hg19: chr7-2291399;