NM_007083.5:c.626G>A

Variant names:

• chr4-122893153-C-T
• rs1048201
• NM_007083.5:c.626G>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.626G>A​(p.Arg209Gln) variant causes a missense change. The variant allele was found at a frequency of 0.188 in 1,613,870 control chromosomes in the GnomAD database, including 32,714 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R209L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.16 (2452 hom., cov: 32)
  • Exomes 𝑓: 0.19 (30262 hom.)
• Consequence: NUDT6 NM_007083.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.09
• Publications: 56 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]

FGF2 (HGNC:3676): (fibroblast growth factor 2) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055366755).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 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.626G>A	p.Arg209Gln	missense	Exon 5 of 5	NP_009014.2
	FGF2	NM_001361665.2	MANE Select	c.*757C>T		3_prime_UTR	Exon 3 of 3	NP_001348594.1	D9ZGF5
	NUDT6	NM_198041.3		c.119G>A	p.Arg40Gln	missense	Exon 5 of 5	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.626G>A	p.Arg209Gln	missense	Exon 5 of 5	ENSP00000306070.5	P53370-1
	NUDT6	ENST00000339154.6	TSL:1	c.119G>A	p.Arg40Gln	missense	Exon 5 of 5	ENSP00000344011.2	P53370-2
	FGF2	ENST00000644866.2	MANE Select	c.*757C>T		3_prime_UTR	Exon 3 of 3	ENSP00000494222.1	P09038-2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24297 AN: 151994 Hom.: 2452 Cov.: 32

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.211 AC: 52742 AN: 250426 AF XY: 0.220

Gnomad AFR exome AF: 0.0562

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.471

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.191 AC: 279367 AN: 1461756 Hom.: 30262 Cov.: 33 AF XY: 0.197 AC XY: 143040 AN XY: 727178

African (AFR) AF: 0.0525 AC: 1758 AN: 33480

American (AMR) AF: 0.156 AC: 6957 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 5028 AN: 26134

East Asian (EAS) AF: 0.467 AC: 18547 AN: 39698

South Asian (SAS) AF: 0.370 AC: 31883 AN: 86254

European-Finnish (FIN) AF: 0.193 AC: 10332 AN: 53396

Middle Eastern (MID) AF: 0.178 AC: 1024 AN: 5768

European-Non Finnish (NFE) AF: 0.173 AC: 192281 AN: 1111914

Other (OTH) AF: 0.191 AC: 11557 AN: 60388

GnomAD4 genome AF: 0.160 AC: 24308 AN: 152114 Hom.: 2452 Cov.: 32 AF XY: 0.169 AC XY: 12601 AN XY: 74362

African (AFR) AF: 0.0580 AC: 2406 AN: 41516

American (AMR) AF: 0.177 AC: 2698 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 685 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2325 AN: 5168

South Asian (SAS) AF: 0.367 AC: 1769 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2158 AN: 10572

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11691 AN: 67976

Other (OTH) AF: 0.145 AC: 305 AN: 2110

Alfa AF: 0.170 Hom.: 8459

Bravo AF: 0.146

TwinsUK AF: 0.169 AC: 628

ALSPAC AF: 0.167 AC: 645

ESP6500AA AF: 0.0656 AC: 289

ESP6500EA AF: 0.175 AC: 1501

ExAC AF: 0.208 AC: 25309

Asia WGS AF: 0.334 AC: 1161 AN: 3478

EpiCase AF: 0.172

EpiControl AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.52
MPC		0.54
ClinPred		0.037	T
GERP RS		5.4
Varity_R		0.96
gMVP		0.82
Mutation Taster		=64/36	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: rs1048201; hg19: chr4-123814308; COSMIC: COSV52648483; COSMIC: COSV52648483;