Genetic Variant NM_004289.7:c.337G>T (chr7-26152835-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004289.7(NFE2L3):c.337G>T(p.Val113Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,326,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

NFE2L3
NM_004289.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33932257).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004289.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L3	NM_004289.7	MANE Select	c.337G>T	p.Val113Leu	missense	Exon 1 of 4	NP_004280.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFE2L3	ENST00000056233.4	TSL:1 MANE Select	c.337G>T	p.Val113Leu	missense	Exon 1 of 4	ENSP00000056233.3	Q9Y4A8
NFE2L3	ENST00000927668.1		c.337G>T	p.Val113Leu	missense	Exon 1 of 4	ENSP00000597727.1
NFE2L3	ENST00000927666.1		c.337G>T	p.Val113Leu	missense	Exon 1 of 4	ENSP00000597725.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

80792

AF XY:

0.0000216

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000619

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:

0.00000226

AC:

AN:

1326428

Hom.:

Cov.:

AF XY:

0.00000306

AC XY:

AN XY:

654118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26824

American (AMR)

AF:

0.000110

AC:

AN:

27216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23488

East Asian (EAS)

AF:

0.00

AC:

AN:

28868

South Asian (SAS)

AF:

0.00

AC:

AN:

73476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3924

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1054548

Other (OTH)

AF:

0.00

AC:

AN:

55132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

-0.072

Eigen_PC

Benign

-0.0091

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.2

PhyloP100

2.4

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.5

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.021

Polyphen

0.36

Vest4

0.49

MutPred

0.38

Loss of sheet (P = 0.0357)

MVP

0.30

MPC

1.9

ClinPred

0.76

GERP RS

3.4

Varity_R

0.62

gMVP

0.52

Mutation Taster

=89/11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over