NM_007083.5:c.626G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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.

Frequency

Genomes: 𝑓 0.16 ( 2452 hom., cov: 32)

Exomes 𝑓: 0.19 ( 30262 hom. )

Consequence

NUDT6
NM_007083.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.09

Publications

56 publications found

Variant links:

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 links:

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]

FGF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT6	NM_007083.5 link	c.626G>A	p.Arg209Gln	missense_variant	Exon 5 of 5	ENST00000304430.10	NP_009014.2	P53370-1
FGF2	NM_001361665.2 link	c.*757C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000644866.2	NP_001348594.1
NUDT6	NM_198041.3 link	c.119G>A	p.Arg40Gln	missense_variant	Exon 5 of 5		NP_932158.1	P53370-2B4DG76
FGF2	NM_002006.6 link	c.*757C>T		3_prime_UTR_variant	Exon 3 of 3		NP_001997.5	P09038-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT6	ENST00000304430.10 link	c.626G>A	p.Arg209Gln	missense_variant	Exon 5 of 5	1	NM_007083.5	ENSP00000306070.5		P53370-1
FGF2	ENST00000644866.2 link	c.*757C>T		3_prime_UTR_variant	Exon 3 of 3		NM_001361665.2	ENSP00000494222.1		P09038-2

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24297

AN:

151994

Hom.:

2452

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.197

AC XY:

143040

AN XY:

727178

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

11950

23900

35849

47799

59749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7002

14004

21006

28008

35010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.160

AC:

24308

AN:

152114

Hom.:

2452

Cov.:

AF XY:

0.169

AC XY:

12601

AN XY:

74362

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11691

AN:

67976

Other (OTH)

AF:

0.145

AC:

305

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1024

2048

3071

4095

5119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

T;.;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;.;T

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.0

M;.;.

PhyloP100

7.1

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.52

MPC

0.54

ClinPred

0.037

GERP RS

5.4

Varity_R

0.96

gMVP

0.82

Mutation Taster

=64/36

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over