Variant 13-110615771-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242882.2(NAXD):c.46+124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000716 in 1,396,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NAXD
NM_001242882.2 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.193

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0951176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAXD	NM_001242882.2 linkuse as main transcript	c.46+124G>A		intron_variant		ENST00000680254.1
NAXD-AS1	NR_182301.1 linkuse as main transcript	n.583C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAXD	ENST00000680254.1 linkuse as main transcript	c.46+124G>A		intron_variant			NM_001242882.2	P2
NAXD-AS1	ENST00000611744.1 linkuse as main transcript	n.583C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1244038

Hom.:

Cov.:

AF XY:

0.00000660

AC XY:

AN XY:

605816

show subpopulations

Gnomad4 AFR exome

AF:

0.000193

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000196

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000567

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 27, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with NAXD-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 33 of the NAXD protein (p.Ala33Thr). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.50

M_CAP

Benign

0.015

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.22

REVEL

Benign

0.063

Sift

Benign

0.043

Sift4G

Uncertain

0.013

Polyphen

0.83

Vest4

0.11

MutPred

0.48

Loss of helix (P = 0.0167);

MVP

0.072

MPC

0.26

ClinPred

0.30

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over