Genetic Variant NFE2L3:p.Ala132Val (chr7-26152893-C-T) – 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_004289.7(NFE2L3):c.395C>T(p.Ala132Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NFE2L3
NM_004289.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.449

Publications

0 publications found

Variant links:

Genes affected

NFE2L3 (HGNC:7783): (NFE2 like bZIP transcription factor 3) This gene encodes a member of the cap 'n' collar basic-region leucine zipper family of transcription factors. The encoded protein heterodimerizes with small musculoaponeurotic fibrosarcoma factors to bind antioxidant response elements in target genes. This protein is a membrane bound glycoprotein that is targeted to the endoplasmic reticulum and the nuclear envelope. Pseudogenes of this gene are found on chromosomes 16, 17, and 18. [provided by RefSeq, Mar 2009]

NFE2L3 links:

Genome browser will be placed here

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=0.13516164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L3	NM_004289.7 link	c.395C>T	p.Ala132Val	missense_variant	Exon 1 of 4	ENST00000056233.4	NP_004280.5	Q9Y4A8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L3	ENST00000056233.4 link	c.395C>T	p.Ala132Val	missense_variant	Exon 1 of 4	1	NM_004289.7	ENSP00000056233.3		Q9Y4A8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1298606

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

639380

African (AFR)

AF:

0.00

AC:

AN:

25802

American (AMR)

AF:

0.00

AC:

AN:

20456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21842

East Asian (EAS)

AF:

0.00

AC:

AN:

28304

South Asian (SAS)

AF:

0.00

AC:

AN:

68162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3818

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1044062

Other (OTH)

AF:

0.00

AC:

AN:

53820

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 30, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.395C>T (p.A132V) alteration is located in exon 1 (coding exon 1) of the NFE2L3 gene. This alteration results from a C to T substitution at nucleotide position 395, causing the alanine (A) at amino acid position 132 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.59

M_CAP

Benign

0.0017

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.45

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.82

REVEL

Benign

0.028

Sift

Benign

0.11

Sift4G

Benign

0.19

Polyphen

0.84

Vest4

0.14

MutPred

0.29

Gain of loop (P = 0.0312);

MVP

0.33

MPC

0.90

ClinPred

0.61

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.042

gMVP

0.21

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over