Genetic Variant NM_001242882.2:c.46G>A (chr13-110615647-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242882.2(NAXD):c.46G>A(p.Val16Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,351,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

NAXD
NM_001242882.2 missense, splice_region

Scores

Splicing: ADA: 0.05108

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 1.83

Publications

0 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 links:

NAXD-AS1 (HGNC:56341): (NAXD antisense RNA 1)

NAXD-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12421623).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
NAXD	NM_001242882.2	MANE Select	c.46G>A	p.Val16Ile	missense splice_region	Exon 1 of 10	NP_001229811.1	A0A7P0T9D8
NAXD	NM_001242883.2		c.56G>A	p.Ser19Asn	missense splice_region	Exon 1 of 7	NP_001229812.1	Q8IW45-4
NAXD	NM_018210.4		c.-28G>A		5_prime_UTR	Exon 1 of 10	NP_060680.2	Q8IW45-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAXD	ENST00000680254.1	MANE Select	c.46G>A	p.Val16Ile	missense splice_region	Exon 1 of 10	ENSP00000505619.1	A0A7P0T9D8
NAXD	ENST00000679389.1		c.46G>A	p.Val16Ile	missense splice_region	Exon 1 of 10	ENSP00000505318.1	A0A7P0T906
NAXD	ENST00000957157.1		c.46G>A	p.Val16Ile	missense splice_region	Exon 1 of 11	ENSP00000627216.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.40e-7

AC:

AN:

1351366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28106

American (AMR)

AF:

0.00

AC:

AN:

31244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23896

East Asian (EAS)

AF:

0.00

AC:

AN:

30092

South Asian (SAS)

AF:

0.00

AC:

AN:

76580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5592

European-Non Finnish (NFE)

AF:

9.40e-7

AC:

AN:

1063818

Other (OTH)

AF:

0.00

AC:

AN:

56090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

NAD(P)HX dehydratase deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.36

M_CAP

Benign

0.047

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

1.8

PROVEAN

Benign

-0.15

REVEL

Benign

0.057

Sift

Benign

0.030

Sift4G

Benign

0.49

Polyphen

0.0040

Vest4

0.12

MutPred

0.45

Loss of helix (P = 0.0123)

MVP

0.30

ClinPred

0.40

GERP RS

2.4

PromoterAI

-0.43

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.051

dbscSNV1_RF

Benign

0.19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over