4-122905625-T-C

Position:

• chr4-122905625-T-C

Variant summary

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

The NM_007083.5(NUDT6):​c.498+6943A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,194 control chromosomes in the GnomAD database, including 50,456 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 0.80 (50456 hom., cov: 32)
• Consequence: NUDT6 NM_007083.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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]

NUDT6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT6	NM_007083.5	c.498+6943A>G		intron_variant		ENST00000304430.10	NP_009014.2
NUDT6	NM_198041.3	c.-10+6943A>G		intron_variant			NP_932158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT6	ENST00000304430.10	c.498+6943A>G		intron_variant		1	NM_007083.5	ENSP00000306070.5

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121280 AN: 152076 Hom.: 50439 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.797 AC: 121340 AN: 152194 Hom.: 50456 Cov.: 32 AF XY: 0.797 AC XY: 59306 AN XY: 74418

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.805

Alfa AF: 0.877 Hom.: 56520

Bravo AF: 0.776

Asia WGS AF: 0.823 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.3
DANN	Benign	0.69

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: rs11737764; hg19: chr4-123826780;