chr4-122921069-C-T

Variant names:

• chr4-122921069-C-T
• rs2125449
• NM_007083.5:c.238+1266G>A

Variant summary

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

The NM_007083.5(NUDT6):​c.238+1266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,080 control chromosomes in the GnomAD database, including 16,878 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 (16877 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: NUDT6 NM_007083.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 1 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=-0.83).
• 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 rank	MANE	Protein	UniProt
NUDT6	NM_007083.5	c.238+1266G>A		intron_variant	Intron 1 of 4	ENST00000304430.10	NP_009014.2
NUDT6	NM_198041.3	c.-270+1732G>A		intron_variant	Intron 1 of 4		NP_932158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT6	ENST00000304430.10	c.238+1266G>A		intron_variant	Intron 1 of 4	1	NM_007083.5	ENSP00000306070.5

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65129 AN: 151960 Hom.: 16872 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.428 AC: 65142 AN: 152078 Hom.: 16877 Cov.: 31 AF XY: 0.426 AC XY: 31667 AN XY: 74338

African (AFR) AF: 0.125 AC: 5178 AN: 41506

American (AMR) AF: 0.492 AC: 7524 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3470

East Asian (EAS) AF: 0.494 AC: 2557 AN: 5172

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4814

European-Finnish (FIN) AF: 0.597 AC: 6315 AN: 10572

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38908 AN: 67950

Other (OTH) AF: 0.454 AC: 958 AN: 2112

Alfa AF: 0.504 Hom.: 18837

Bravo AF: 0.413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.77
PhyloP100		0.55
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: rs2125449; hg19: chr4-123842224;