dbSNP rs1210033418: NFE2L3:p.Phe102Cys (chr7-26152803-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004289.7(NFE2L3):c.305T>G(p.Phe102Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,335,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

NFE2L3
NM_004289.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.261

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L3	NM_004289.7 link	c.305T>G	p.Phe102Cys	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.305T>G	p.Phe102Cys	missense_variant	Exon 1 of 4	1	NM_004289.7	ENSP00000056233.3		Q9Y4A8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000116

AC:

AN:

85966

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000375

AC:

AN:

1335102

Hom.:

Cov.:

AF XY:

0.00000456

AC XY:

AN XY:

658282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27040

American (AMR)

AF:

0.00

AC:

AN:

29218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23748

East Asian (EAS)

AF:

0.00

AC:

AN:

29588

South Asian (SAS)

AF:

0.0000538

AC:

AN:

74394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3942

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1058458

Other (OTH)

AF:

0.0000180

AC:

AN:

55624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.305T>G (p.F102C) alteration is located in exon 1 (coding exon 1) of the NFE2L3 gene. This alteration results from a T to G substitution at nucleotide position 305, causing the phenylalanine (F) at amino acid position 102 to be replaced by a cysteine (C). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

0.17

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.2

PhyloP100

0.26

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Benign

0.058

Sift4G

Benign

0.089

Polyphen

0.99

Vest4

0.59

MutPred

0.32

Gain of catalytic residue at P101 (P = 0.0073);

MVP

0.48

MPC

2.3

ClinPred

0.75

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.43

Mutation Taster

=95/5

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.

rs1210033418

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over