NM_006164.5:c.91G>T

Variant names:

• chr2-177234226-C-A
• rs1553488015
• NM_006164.5:c.91G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_006164.5(NFE2L2):​c.91G>T​(p.Gly31*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

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]

NFE2L2 Gene-Disease associations (from GenCC):

• immunodeficiency, developmental delay, and hypohomocysteinemia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Illumina, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006164.5. 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
	NFE2L2	NM_006164.5	MANE Select	c.91G>T	p.Gly31*	stop_gained	Exon 2 of 5	NP_006155.2
	NFE2L2	NM_001313904.1		c.-139G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001300833.1
	NFE2L2	NM_001145412.3		c.43G>T	p.Gly15*	stop_gained	Exon 2 of 5	NP_001138884.1	Q16236-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000397062.8	TSL:1 MANE Select	c.91G>T	p.Gly31*	stop_gained	Exon 2 of 5	ENSP00000380252.3	Q16236-1
	NFE2L2	ENST00000397063.9	TSL:1	c.43G>T	p.Gly15*	stop_gained	Exon 2 of 5	ENSP00000380253.4	Q16236-2
	NFE2L2	ENST00000421929.6	TSL:1	c.43G>T	p.Gly15*	stop_gained	Exon 2 of 5	ENSP00000412191.2	Q16236-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.6
Vest4		0.85
GERP RS		5.8
Mutation Taster		=6/194	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553488015; hg19: chr2-178098954;