rs886043551
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM2PM5BP4
The NM_006158.5(NEFL):c.22C>T(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8R) has been classified as Pathogenic.
Frequency
Consequence
NM_006158.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEFL | NM_006158.5 | c.22C>T | p.Pro8Ser | missense_variant | 1/4 | ENST00000610854.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.22C>T | p.Pro8Ser | missense_variant | 1/4 | 1 | NM_006158.5 | P1 | |
ENST00000607735.2 | n.554G>A | non_coding_transcript_exon_variant | 1/1 | ||||||
NEFL | ENST00000615973.1 | n.228C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1447044Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 718418
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2E Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 14, 2020 | 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. This variant disrupts the p.Pro8 amino acid residue in NEFL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22155564, 12566280, 28501821, 23618875, 19158810). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with NEFL-related conditions. ClinVar contains an entry for this variant (Variation ID: 576990). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 8 of the NEFL protein (p.Pro8Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 03, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at