chr7-26153048-G-C

Variant names:

• chr7-26153048-G-C
• rs979453397
• NM_004289.7:c.550G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004289.7(NFE2L3):​c.550G>C​(p.Ala184Pro) 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. 12/21 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 𝑓: 7.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFE2L3 NM_004289.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20234114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L3	NM_004289.7	c.550G>C	p.Ala184Pro	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.550G>C	p.Ala184Pro	missense_variant	Exon 1 of 4	1	NM_004289.7	ENSP00000056233.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000840 AC: 1 AN: 119090 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65868

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000430

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.28e-7 AC: 1 AN: 1374368 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 678096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000288

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Benign	0.20	T
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.090
MutPred		0.086		Loss of catalytic residue at A184 (P = 0.191);
MVP		0.32
MPC		1.4
ClinPred		0.47	T
GERP RS		2.8
Varity_R		0.12
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs979453397; hg19: chr7-26192668;