NM_006164.5:c.1769A>T

Variant names:

• chr2-177230834-T-A
• rs747640258
• NM_006164.5:c.1769A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006164.5(NFE2L2):​c.1769A>T​(p.Asn590Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NFE2L2 NM_006164.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

Genes affected

NFE2L2 (HGNC:7782): (NFE2 like bZIP transcription factor 2) This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
NFE2L2	NM_006164.5	c.1769A>T	p.Asn590Ile	missense_variant	Exon 5 of 5	ENST00000397062.8	NP_006155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8	c.1769A>T	p.Asn590Ile	missense_variant	Exon 5 of 5	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	.;D;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	.;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.9	D;D;D;.
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D;D;.
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.80	.;P;.;.
Vest4		0.65
MutPred		0.28		.;Loss of disorder (P = 0.0087);.;.;
MVP		0.35
MPC		0.33
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.59

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

Other links and lift over

dbSNP: rs747640258; hg19: chr2-178095562;