NM_003204.3:c.37C>T

Variant names:

• chr17-48051155-C-T
• NM_003204.3:c.37C>T

Variant summary

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

The NM_003204.3(NFE2L1):​c.37C>T​(p.Leu13Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NFE2L1 NM_003204.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56
• 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.37C>T	p.Leu13Phe	missense	Exon 2 of 6	NP_003195.1	Q14494-1
	NFE2L1	NM_001439152.1		c.37C>T	p.Leu13Phe	missense	Exon 2 of 6	NP_001426081.1
	NFE2L1	NM_001330261.2		c.37C>T	p.Leu13Phe	missense	Exon 2 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.37C>T	p.Leu13Phe	missense	Exon 2 of 6	ENSP00000354855.3	Q14494-1
	NFE2L1	ENST00000357480.9	TSL:1	c.37C>T	p.Leu13Phe	missense	Exon 2 of 5	ENSP00000350072.5	Q14494-2
	NFE2L1	ENST00000585291.5	TSL:1	c.37C>T	p.Leu13Phe	missense	Exon 3 of 6	ENSP00000461960.1	Q14494-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	34
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
PhyloP100		4.6
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.87	P
Vest4		0.36
MutPred		0.24		Loss of helix (P = 0.2271)
MVP		0.24
MPC		0.66
ClinPred		0.65	D
GERP RS		2.8
Varity_R		0.19
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 6

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

Other links and lift over

hg19: chr17-46128517; COSMIC: COSV100671760; COSMIC: COSV100671760;