rs898091

chr4-122918909-G-A

Variant summary

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

The NM_007083.5(NUDT6):c.239-1205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,264 control chromosomes in the GnomAD database, including 56,711 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 0.86 (56709 hom., cov: 33)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: NUDT6 NM_007083.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT6	NM_007083.5	c.239-1205C>T		intron_variant		ENST00000304430.10
NUDT6	NM_198041.3	c.-269-1205C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT6	ENST00000304430.10	c.239-1205C>T		intron_variant		1	NM_007083.5	P1

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130288 AN: 152142 Hom.: 56672 Cov.: 33

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.857

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.856 AC: 130382 AN: 152260 Hom.: 56709 Cov.: 33 AF XY: 0.856 AC XY: 63740 AN XY: 74450

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.926

Gnomad4 NFE AF: 0.936

Gnomad4 OTH AF: 0.859

Alfa AF: 0.917 Hom.: 86531

Bravo AF: 0.839

Asia WGS AF: 0.929 AC: 3232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.032
Dann	Benign	0.64

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: rs898091; hg19: chr4-123840064;