NM_003204.3:c.589C>G

Variant names:

• chr17-48056464-C-G
• rs372251551
• NM_003204.3:c.589C>G

Variant summary

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

The NM_003204.3(NFE2L1):​c.589C>G​(p.Arg197Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R197H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NFE2L1 NM_003204.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

Genes affected

NFE2L1 (HGNC:7781): (NFE2 like bZIP transcription factor 1) This gene encodes a protein that is involved in globin gene expression in erythrocytes. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene, NFE2L1, and for "nuclear respiratory factor 1" which has an official symbol of NRF1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003204.3. 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
	NFE2L1	NM_003204.3	MANE Select	c.589C>G	p.Arg197Gly	missense	Exon 3 of 6	NP_003195.1	Q14494-1
	NFE2L1	NM_001439152.1		c.589C>G	p.Arg197Gly	missense	Exon 3 of 6	NP_001426081.1
	NFE2L1	NM_001330261.2		c.556C>G	p.Arg186Gly	missense	Exon 3 of 6	NP_001317190.1	J9JIE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L1	ENST00000362042.8	TSL:1 MANE Select	c.589C>G	p.Arg197Gly	missense	Exon 3 of 6	ENSP00000354855.3	Q14494-1
	NFE2L1	ENST00000357480.9	TSL:1	c.589C>G	p.Arg197Gly	missense	Exon 3 of 5	ENSP00000350072.5	Q14494-2
	NFE2L1	ENST00000585291.5	TSL:1	c.589C>G	p.Arg197Gly	missense	Exon 4 of 6	ENSP00000461960.1	Q14494-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.045	D
Polyphen		0.89	P
Vest4		0.69
MutPred		0.56		Gain of relative solvent accessibility (P = 0.0507)
MVP		0.68
MPC		1.4
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.57
gMVP		0.57

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: rs372251551; hg19: chr17-46133826;