dbSNP rs3742193: NAXD:c.441+108T>C (chr13-110627655-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.441+108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 723,468 control chromosomes in the GnomAD database, including 8,163 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 0.15 ( 2084 hom., cov: 33)

Exomes 𝑓: 0.13 ( 6079 hom. )

Consequence

NAXD
NM_001242882.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

5 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=-0.97).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAXD	NM_001242882.2 link	c.441+108T>C		intron_variant	Intron 5 of 9	ENST00000680254.1	NP_001229811.1	Q8IW45A0A7P0T9D8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAXD	ENST00000680254.1 link	c.441+108T>C		intron_variant	Intron 5 of 9		NM_001242882.2	ENSP00000505619.1		A0A7P0T9D8

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23100

AN:

152122

Hom.:

2059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.144

GnomAD4 exome

AF:

0.134

AC:

76315

AN:

571230

Hom.:

6079

AF XY:

0.132

AC XY:

39567

AN XY:

300712

show subpopulations

African (AFR)

AF:

0.177

AC:

2786

AN:

15770

American (AMR)

AF:

0.352

AC:

10241

AN:

29122

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

2440

AN:

16382

East Asian (EAS)

AF:

0.141

AC:

4592

AN:

32642

South Asian (SAS)

AF:

0.126

AC:

6809

AN:

53912

European-Finnish (FIN)

AF:

0.103

AC:

4549

AN:

44072

Middle Eastern (MID)

AF:

0.115

AC:

333

AN:

2900

European-Non Finnish (NFE)

AF:

0.117

AC:

40434

AN:

346372

Other (OTH)

AF:

0.137

AC:

4131

AN:

30058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3091

6182

9272

12363

15454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.152

AC:

23175

AN:

152238

Hom.:

2084

Cov.:

AF XY:

0.154

AC XY:

11454

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.181

AC:

7526

AN:

41554

American (AMR)

AF:

0.266

AC:

4060

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

539

AN:

3470

East Asian (EAS)

AF:

0.146

AC:

755

AN:

5174

South Asian (SAS)

AF:

0.125

AC:

604

AN:

4826

European-Finnish (FIN)

AF:

0.108

AC:

1141

AN:

10608

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8155

AN:

67998

Other (OTH)

AF:

0.142

AC:

300

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1022

2045

3067

4090

5112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.133

Hom.:

2590

Bravo

AF:

0.167

Asia WGS

AF:

0.115

AC:

400

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.79

(source)

DANN

Benign

0.37

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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