Variant 1-156591824-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144772.3(NAXE):c.20T>C(p.Leu7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NAXE
NM_144772.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

NAXE (HGNC:18453): (NAD(P)HX epimerase) The product of this gene interacts with apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoproteins (HDLs). It is secreted into some bodily fluids, and its synthesis and secretion are stimulated in vitro by incubating cells with apoA-I. The human genome contains related pseudogenes. [provided by RefSeq, Jul 2008]

NAXE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAXE	NM_144772.3 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	1/6	ENST00000368235.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAXE	ENST00000368235.8 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	1/6	1	NM_144772.3	P1	Q8NCW5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722936

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Invitae

Aug 28, 2023

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1367726). This variant has not been reported in the literature in individuals affected with NAXE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 7 of the NAXE protein (p.Leu7Pro). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

Cadd

Benign

Dann

Benign

0.84

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.49

T;T;T

M_CAP

Uncertain

0.29

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-0.47

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.8

N;N;N

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.69

MutPred

0.68

Loss of helix (P = 3e-04);Loss of helix (P = 3e-04);Loss of helix (P = 3e-04);

MVP

0.60

MPC

0.50

ClinPred

0.93

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.77

gMVP

0.95

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over