Genetic Variant NM_001242882.2:c.*747G>A (chr13-110639275-G-A) – 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.*747G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 155,342 control chromosomes in the GnomAD database, including 1,082 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 0.11 ( 1073 hom., cov: 33)

Exomes 𝑓: 0.057 ( 9 hom. )

Consequence

NAXD
NM_001242882.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.952

Publications

10 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=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAXD	NM_001242882.2 link	c.*747G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000680254.1	NP_001229811.1	Q8IW45A0A7P0T9D8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAXD	ENST00000680254.1 link	c.*747G>A		3_prime_UTR_variant	Exon 10 of 10		NM_001242882.2	ENSP00000505619.1		A0A7P0T9D8

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17097

AN:

152038

Hom.:

1073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0612

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0580

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.126

GnomAD4 exome

AF:

0.0568

AC:

181

AN:

3186

Hom.:

Cov.:

AF XY:

0.0582

AC XY:

AN XY:

1700

show subpopulations

African (AFR)

AF:

0.0417

AC:

AN:

American (AMR)

AF:

0.0361

AC:

AN:

638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0147

AC:

AN:

South Asian (SAS)

AF:

0.0243

AC:

AN:

288

European-Finnish (FIN)

AF:

0.0769

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0707

AC:

144

AN:

2038

Other (OTH)

AF:

0.0357

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.112

AC:

17090

AN:

152156

Hom.:

1073

Cov.:

AF XY:

0.114

AC XY:

8441

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0611

AC:

2536

AN:

41534

American (AMR)

AF:

0.104

AC:

1592

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

446

AN:

3468

East Asian (EAS)

AF:

0.103

AC:

534

AN:

5170

South Asian (SAS)

AF:

0.0583

AC:

281

AN:

4820

European-Finnish (FIN)

AF:

0.198

AC:

2096

AN:

10578

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9125

AN:

67998

Other (OTH)

AF:

0.125

AC:

264

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

763

1526

2290

3053

3816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.0917

Hom.:

168

Bravo

AF:

0.105

Asia WGS

AF:

0.0840

AC:

294

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.0

(source)

DANN

Benign

0.60

PhyloP100

-0.95

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