rs59443585
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM1PM2PM5PP2PP3
The NM_006158.5(NEFL):c.995A>T(p.Gln332Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. Q332P) has been classified as Pathogenic.
Frequency
Consequence
NM_006158.5 missense
Scores
Clinical Significance
Conservation
Publications
- Charcot-Marie-Tooth diseaseInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- Charcot-Marie-Tooth disease type 2Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Charcot-Marie-Tooth disease type 1FInheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- Charcot-Marie-Tooth disease type 2EInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Charcot-Marie-Tooth disease type 2B5Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.995A>T | p.Gln332Leu | missense_variant | Exon 1 of 4 | 1 | NM_006158.5 | ENSP00000482169.2 | ||
NEFL | ENST00000615973.1 | n.1201A>T | non_coding_transcript_exon_variant | Exon 1 of 1 | 6 | |||||
ENSG00000272157 | ENST00000607735.3 | n.-170T>A | upstream_gene_variant | 6 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 37
GnomAD4 genome Cov.: 31
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at