Genetic Variant NM_001242882.2:c.*169T>C (chr13-110638697-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001242882.2(NAXD):c.*169T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 798,342 control chromosomes in the GnomAD database, including 35,964 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 0.31 ( 7772 hom., cov: 33)

Exomes 𝑓: 0.28 ( 28192 hom. )

Consequence

NAXD
NM_001242882.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.386

Publications

13 publications found

Variant links:

Genes affected

NAXD (HGNC:25576): (NAD(P)HX dehydratase) Enables ATP-dependent NAD(P)H-hydrate dehydratase activity. Predicted to be involved in metabolite repair. Predicted to be located in cytosol; endoplasmic reticulum; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

NAXD Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
NAD(P)HX dehydratase deficiency
Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: Baylor College of Medicine Research Center, Ambry Genetics

NAXD 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 (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAXD	NM_001242882.2 link	c.*169T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000680254.1	NP_001229811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAXD	ENST00000680254.1 link	c.*169T>C		3_prime_UTR_variant	Exon 10 of 10		NM_001242882.2	ENSP00000505619.1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47781

AN:

151940

Hom.:

7752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.307

GnomAD2 exomes

AF:

0.339

AC:

45407

AN:

133850

AF XY:

0.329

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.535

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.308

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.285

AC:

183949

AN:

646284

Hom.:

28192

Cov.:

AF XY:

0.284

AC XY:

97995

AN XY:

344450

show subpopulations

African (AFR)

AF:

0.353

AC:

6141

AN:

17378

American (AMR)

AF:

0.517

AC:

18028

AN:

34892

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

6167

AN:

20602

East Asian (EAS)

AF:

0.306

AC:

9968

AN:

32580

South Asian (SAS)

AF:

0.318

AC:

20378

AN:

64096

European-Finnish (FIN)

AF:

0.315

AC:

10508

AN:

33408

Middle Eastern (MID)

AF:

0.304

AC:

1306

AN:

4290

European-Non Finnish (NFE)

AF:

0.250

AC:

101490

AN:

405270

Other (OTH)

AF:

0.295

AC:

9963

AN:

33768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

6912

13824

20735

27647

34559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1318

2636

3954

5272

6590

<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:

0.315

AC:

47843

AN:

152058

Hom.:

7772

Cov.:

AF XY:

0.319

AC XY:

23727

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.353

AC:

14640

AN:

41468

American (AMR)

AF:

0.435

AC:

6645

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1079

AN:

3472

East Asian (EAS)

AF:

0.310

AC:

1608

AN:

5182

South Asian (SAS)

AF:

0.320

AC:

1542

AN:

4822

European-Finnish (FIN)

AF:

0.312

AC:

3291

AN:

10548

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18062

AN:

67970

Other (OTH)

AF:

0.307

AC:

648

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1668

3335

5003

6670

8338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.294

Hom.:

9318

Bravo

AF:

0.329

Asia WGS

AF:

0.298

AC:

1039

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.6

(source)

DANN

Benign

0.41

PhyloP100

0.39

Mutation Taster

=100/0

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