19-13135340-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP2PP3_StrongPP5
The ENST00000292431.5(NACC1):c.133C>T(p.Arg45Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R45Q) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000292431.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NACC1 | NM_052876.4 | c.133C>T | p.Arg45Trp | missense_variant | 2/6 | ENST00000292431.5 | NP_443108.1 | |
NACC1 | XM_005259721.4 | c.133C>T | p.Arg45Trp | missense_variant | 3/7 | XP_005259778.1 | ||
NACC1 | XM_047438118.1 | c.133C>T | p.Arg45Trp | missense_variant | 2/6 | XP_047294074.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NACC1 | ENST00000292431.5 | c.133C>T | p.Arg45Trp | missense_variant | 2/6 | 1 | NM_052876.4 | ENSP00000292431 | P1 | |
NACC1 | ENST00000586171.3 | c.133C>T | p.Arg45Trp | missense_variant | 3/7 | 5 | ENSP00000467120 | P1 | ||
NACC1 | ENST00000700232.1 | c.133C>T | p.Arg45Trp | missense_variant | 2/6 | ENSP00000514870 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461324Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726984
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33057194, 35982159) - |
Neurodevelopmental disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes | Nov 03, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at