rs886041064

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The NM_144772.3(NAXE):​c.653A>T​(p.Asp218Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NAXE
NM_144772.3 missense

Scores

13
5
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.21
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity NNRE_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.988
PP5
Variant 1-156593544-A-T is Pathogenic according to our data. Variant chr1-156593544-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 268121.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-156593544-A-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAXENM_144772.3 linkuse as main transcriptc.653A>T p.Asp218Val missense_variant 5/6 ENST00000368235.8 NP_658985.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAXEENST00000368235.8 linkuse as main transcriptc.653A>T p.Asp218Val missense_variant 5/61 NM_144772.3 ENSP00000357218 P1Q8NCW5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461882
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMNov 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.94
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Pathogenic
0.30
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Uncertain
0.69
D
MutationAssessor
Pathogenic
4.7
H;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-8.3
D;D
REVEL
Pathogenic
0.92
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;D
Vest4
0.99
MutPred
0.88
Gain of glycosylation at S221 (P = 0.1074);Gain of glycosylation at S221 (P = 0.1074);
MVP
0.85
MPC
1.3
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.91
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs886041064; hg19: chr1-156563336; API