4-122905625-T-C

Variant names:

• chr4-122905625-T-C
• rs11737764
• NM_007083.5:c.498+6943A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NUDT6	NM_007083.5	c.498+6943A>G		intron_variant	Intron 3 of 4	ENST00000304430.10	NP_009014.2
NUDT6	NM_198041.3	c.-10+6943A>G		intron_variant	Intron 3 of 4		NP_932158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT6	ENST00000304430.10	c.498+6943A>G		intron_variant	Intron 3 of 4	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

African (AFR) AF: 0.544 AC: 22579 AN: 41480

American (AMR) AF: 0.802 AC: 12268 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2927 AN: 3470

East Asian (EAS) AF: 0.950 AC: 4922 AN: 5182

South Asian (SAS) AF: 0.768 AC: 3703 AN: 4820

European-Finnish (FIN) AF: 0.921 AC: 9772 AN: 10610

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62369 AN: 68014

Other (OTH) AF: 0.805 AC: 1700 AN: 2112

Alfa AF: 0.862 Hom.: 72119

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
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11737764; hg19: chr4-123826780;