rs1982569

chr4-122902709-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007083.5(NUDT6):c.499-5031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,000 control chromosomes in the GnomAD database, including 16,895 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 0.43 (16895 hom., cov: 32)
• Consequence: NUDT6 NM_007083.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

Genes affected

NUDT6 (HGNC:8053): (nudix hydrolase 6) This gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT6	NM_007083.5	c.499-5031G>A		intron_variant		ENST00000304430.10
NUDT6	NM_198041.3	c.-9-5031G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT6	ENST00000304430.10	c.499-5031G>A		intron_variant		1	NM_007083.5	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65182 AN: 151880 Hom.: 16889 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.429 AC: 65197 AN: 152000 Hom.: 16895 Cov.: 32 AF XY: 0.426 AC XY: 31659 AN XY: 74270

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.455

Alfa AF: 0.501 Hom.: 2653

Bravo AF: 0.414

Asia WGS AF: 0.418 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	8.9
Dann	Benign	0.67

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: rs1982569; hg19: chr4-123823864;