dbSNP rs963731881: NFE2L3:p.Gly145Ser (chr7-26152931-G-A) – 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.433G>A(p.Gly145Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000777 in 1,287,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G145C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

NFE2L3
NM_004289.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.54

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=0.14322978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L3	NM_004289.7 link	c.433G>A	p.Gly145Ser	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.433G>A	p.Gly145Ser	missense_variant	Exon 1 of 4	1	NM_004289.7	ENSP00000056233.3		Q9Y4A8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.77e-7

AC:

AN:

1287444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

632748

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

25362

American (AMR)

AF:

0.00

AC:

AN:

17562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20658

East Asian (EAS)

AF:

0.00

AC:

AN:

28348

South Asian (SAS)

AF:

0.00

AC:

AN:

65710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3754

European-Non Finnish (NFE)

AF:

9.61e-7

AC:

AN:

1040934

Other (OTH)

AF:

0.00

AC:

AN:

53312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.52

M_CAP

Benign

0.021

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

2.5

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.57

REVEL

Benign

0.042

Sift

Benign

0.33

Sift4G

Benign

0.52

Polyphen

0.90

Vest4

0.14

MutPred

0.13

Gain of glycosylation at G145 (P = 0.0045);

MVP

0.30

MPC

0.95

ClinPred

0.49

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.15

Mutation Taster

=97/3

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.

rs963731881

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over