7-26152974-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004289.7(NFE2L3):ā€‹c.476C>Gā€‹(p.Ala159Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 1,344,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000022 ( 0 hom. )

Consequence

NFE2L3
NM_004289.7 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0110
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059087187).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NFE2L3NM_004289.7 linkc.476C>G p.Ala159Gly 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
NFE2L3ENST00000056233.4 linkc.476C>G p.Ala159Gly missense_variant Exon 1 of 4 1 NM_004289.7 ENSP00000056233.3 Q9Y4A8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000223
AC:
3
AN:
1344366
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
662964
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000993
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
1.8
DANN
Benign
0.83
DEOGEN2
Benign
0.034
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.45
N
REVEL
Benign
0.038
Sift
Benign
0.33
T
Sift4G
Benign
0.38
T
Polyphen
0.31
B
Vest4
0.072
MutPred
0.11
Gain of relative solvent accessibility (P = 0.005);
MVP
0.21
MPC
0.89
ClinPred
0.098
T
GERP RS
-4.8
Varity_R
0.028
gMVP
0.10

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1047779260; hg19: chr7-26192594; API