7-26152580-G-T

Variant names:

• chr7-26152580-G-T
• rs762675027
• NM_004289.7:c.82G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004289.7(NFE2L3):​c.82G>T​(p.Val28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V28I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFE2L3 NM_004289.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10073736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L3	NM_004289.7	c.82G>T	p.Val28Leu	missense_variant	Exon 1 of 4	ENST00000056233.4	NP_004280.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L3	ENST00000056233.4	c.82G>T	p.Val28Leu	missense_variant	Exon 1 of 4	1	NM_004289.7	ENSP00000056233.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1387172 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689486

African (AFR) AF: 0.00 AC: 0 AN: 29006

American (AMR) AF: 0.00 AC: 0 AN: 36598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24506

East Asian (EAS) AF: 0.00 AC: 0 AN: 32490

South Asian (SAS) AF: 0.00 AC: 0 AN: 79502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085344

Other (OTH) AF: 0.00 AC: 0 AN: 57596

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.55
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.0050
Sift	Benign	0.14	T
Sift4G	Benign	0.17	T
Polyphen		0.0050	B
Vest4		0.11
MutPred		0.40		Loss of sheet (P = 0.0315);
MVP		0.12
MPC		0.87
ClinPred		0.13	T
GERP RS		1.5
PromoterAI		0.0017	Neutral
Varity_R		0.072
gMVP		0.37
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs762675027; hg19: chr7-26192200;