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):

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242882.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAXD	NM_001242882.2	MANE Select	c.441+108T>C	intron	N/A	NP_001229811.1	A0A7P0T9D8
NAXD	NM_018210.4		c.495+108T>C	intron	N/A	NP_060680.2	Q8IW45-2
NAXD	NM_001242881.2		c.495+108T>C	intron	N/A	NP_001229810.1	Q8IW45-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAXD	ENST00000680254.1	MANE Select	c.441+108T>C	intron	N/A	ENSP00000505619.1	A0A7P0T9D8
NAXD	ENST00000309957.3	TSL:2	c.495+108T>C	intron	N/A	ENSP00000311984.2	Q8IW45-2
NAXD	ENST00000679389.1		c.441+108T>C	intron	N/A	ENSP00000505318.1	A0A7P0T906

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over