chr4-122918909-G-A

Variant names:

• chr4-122918909-G-A
• rs898091
• NM_007083.5:c.239-1205C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007083.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT6	NM_007083.5	MANE Select	c.239-1205C>T		intron	N/A	NP_009014.2
	NUDT6	NM_198041.3		c.-269-1205C>T		intron	N/A	NP_932158.1	P53370-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT6	ENST00000304430.10	TSL:1 MANE Select	c.239-1205C>T		intron	N/A	ENSP00000306070.5	P53370-1
	NUDT6	ENST00000339154.6	TSL:1	c.-269-1205C>T		intron	N/A	ENSP00000344011.2	P53370-2
	NUDT6	ENST00000510735.1	TSL:5	c.106+3426C>T		intron	N/A	ENSP00000423745.1	H0Y9C0

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

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: 4 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.686 AC: 28467 AN: 41508

American (AMR) AF: 0.845 AC: 12934 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3109 AN: 3472

East Asian (EAS) AF: 0.959 AC: 4975 AN: 5186

South Asian (SAS) AF: 0.914 AC: 4411 AN: 4826

European-Finnish (FIN) AF: 0.926 AC: 9830 AN: 10616

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63696 AN: 68036

Other (OTH) AF: 0.859 AC: 1815 AN: 2112

Alfa AF: 0.908 Hom.: 107631

Bravo AF: 0.839

Asia WGS AF: 0.929 AC: 3232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.032
DANN	Benign	0.64
PhyloP100		-1.1
Mutation Taster		=9/91	disease causing

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: rs898091; hg19: chr4-123840064;