chr7-26185116-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004289.7(NFE2L3):c.1418G>A(p.Ser473Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S473T) has been classified as Benign.
Frequency
Consequence
NM_004289.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFE2L3 | NM_004289.7 | c.1418G>A | p.Ser473Asn | missense_variant | 4/4 | ENST00000056233.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFE2L3 | ENST00000056233.4 | c.1418G>A | p.Ser473Asn | missense_variant | 4/4 | 1 | NM_004289.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000151 AC: 38AN: 251120Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135712
GnomAD4 exome AF: 0.0000732 AC: 107AN: 1461598Hom.: 0 Cov.: 33 AF XY: 0.0000536 AC XY: 39AN XY: 727102
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74478
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2023 | The c.1418G>A (p.S473N) alteration is located in exon 4 (coding exon 4) of the NFE2L3 gene. This alteration results from a G to A substitution at nucleotide position 1418, causing the serine (S) at amino acid position 473 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at