7-26153037-A-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.539A>Gā€‹(p.Gln180Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,526,844 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: š‘“ 0.0000066 ( 0 hom., 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: 0.121
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=0.060789227).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NFE2L3NM_004289.7 linkc.539A>G p.Gln180Arg 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.539A>G p.Gln180Arg missense_variant Exon 1 of 4 1 NM_004289.7 ENSP00000056233.3 Q9Y4A8

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000218
AC:
3
AN:
1374632
Hom.:
0
Cov.:
31
AF XY:
0.00000147
AC XY:
1
AN XY:
678268
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000186
Gnomad4 OTH exome
AF:
0.0000175
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
14
DANN
Benign
0.97
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.041
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.061
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.051
Sift
Benign
0.051
T
Sift4G
Benign
0.071
T
Polyphen
0.0010
B
Vest4
0.049
MutPred
0.10
Loss of glycosylation at P177 (P = 0.2017);
MVP
0.21
MPC
0.96
ClinPred
0.27
T
GERP RS
0.98
Varity_R
0.066
gMVP
0.090

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: rs987478525; hg19: chr7-26192657; API