1-156591859-G-C

Position:

• chr1-156591859-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144772.3(NAXE):​c.55G>C​(p.Val19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 1,611,320 control chromosomes in the GnomAD database, including 747,940 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. V19V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.94 (66835 hom., cov: 34)
  • Exomes 𝑓: 0.97 (681105 hom.)
• Consequence: NAXE NM_144772.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.183

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.675258E-7).
• BP6: Variant 1-156591859-G-C is Benign according to our data. Variant chr1-156591859-G-C is described in ClinVar as [Benign]. Clinvar id is 1167828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAXE	NM_144772.3	c.55G>C	p.Val19Leu	missense_variant	1/6	ENST00000368235.8	NP_658985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAXE	ENST00000368235.8	c.55G>C	p.Val19Leu	missense_variant	1/6	1	NM_144772.3	ENSP00000357218.3

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142321 AN: 152074 Hom.: 66800 Cov.: 34

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.952

GnomAD3 exomes AF: 0.959 AC: 228777 AN: 238506 Hom.: 109825 AF XY: 0.958 AC XY: 126033 AN XY: 131560

Gnomad AFR exome AF: 0.855

Gnomad AMR exome AF: 0.976

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 0.976

Gnomad SAS exome AF: 0.920

Gnomad FIN exome AF: 0.977

Gnomad NFE exome AF: 0.970

Gnomad OTH exome AF: 0.963

GnomAD4 exome AF: 0.966 AC: 1409424 AN: 1459130 Hom.: 681105 Cov.: 101 AF XY: 0.965 AC XY: 700387 AN XY: 725998

Gnomad4 AFR exome AF: 0.853

Gnomad4 AMR exome AF: 0.975

Gnomad4 ASJ exome AF: 0.975

Gnomad4 EAS exome AF: 0.979

Gnomad4 SAS exome AF: 0.921

Gnomad4 FIN exome AF: 0.978

Gnomad4 NFE exome AF: 0.972

Gnomad4 OTH exome AF: 0.960

GnomAD4 genome AF: 0.936 AC: 142412 AN: 152190 Hom.: 66835 Cov.: 34 AF XY: 0.935 AC XY: 69589 AN XY: 74414

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.959

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.979

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.952

Alfa AF: 0.960 Hom.: 22682

Bravo AF: 0.933

TwinsUK AF: 0.971 AC: 3600

ALSPAC AF: 0.969 AC: 3734

ESP6500AA AF: 0.889 AC: 3616

ESP6500EA AF: 0.977 AC: 7986

ExAC AF: 0.956 AC: 112925

Asia WGS AF: 0.933 AC: 3236 AN: 3470

EpiCase AF: 0.963

EpiControl AF: 0.965

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.58
DEOGEN2	Benign	0.019	.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.18	T;T;T
MetaRNN	Benign	8.7e-7	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.6	.;N;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.0	N;N;N
REVEL	Benign	0.054
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.043
MutPred		0.11		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MPC		0.31
ClinPred		0.0035	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.44

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

Other links and lift over

dbSNP: rs7516274; hg19: chr1-156561651; COSMIC: COSV63992221; COSMIC: COSV63992221;