chr8-24955908-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006158.5(NEFL):c.608C>T(p.Ala203Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,744 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A203A) has been classified as Likely benign.
Frequency
Consequence
NM_006158.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEFL | NM_006158.5 | c.608C>T | p.Ala203Val | missense_variant | 1/4 | ENST00000610854.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.608C>T | p.Ala203Val | missense_variant | 1/4 | 1 | NM_006158.5 | P1 | |
NEFL | ENST00000615973.1 | n.814C>T | non_coding_transcript_exon_variant | 1/1 | |||||
ENST00000607735.2 | upstream_gene_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000420 AC: 1AN: 237834Hom.: 0 AF XY: 0.00000765 AC XY: 1AN XY: 130752
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1452744Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 723232
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 24, 2018 | This variant has not been reported in the literature in individuals with NEFL-related disease. This sequence change replaces alanine with valine at codon 203 of the NEFL protein (p.Ala203Val). The alanine residue is highlyconserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs753319598, ExAC 0.002%). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at