8-24955533-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_006158.5(NEFL):c.983C>A(p.Ala328Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006158.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248940Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135090
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461164Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 726886
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2E Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 328 of the NEFL protein (p.Ala328Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. ClinVar contains an entry for this variant (Variation ID: 464930). This variant has not been reported in the literature in individuals affected with NEFL-related conditions. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at