rs730880025
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 9P and 4B. PM5PP2PP3_StrongPP5_ModerateBS2
The NM_006000.3(TUBA4A):c.958C>T(p.Arg320Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R320H) has been classified as Pathogenic.
Frequency
Consequence
NM_006000.3 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 |
---|---|---|---|---|---|---|---|
TUBA4A | NM_006000.3 | c.958C>T | p.Arg320Cys | missense_variant | 4/4 | ENST00000248437.9 | |
TUBA4A | NM_001278552.2 | c.913C>T | p.Arg305Cys | missense_variant | 4/4 | ||
TUBA4A | XM_047445674.1 | c.985C>T | p.Arg329Cys | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA4A | ENST00000248437.9 | c.958C>T | p.Arg320Cys | missense_variant | 4/4 | 1 | NM_006000.3 | P1 | |
TUBA4A | ENST00000392088.6 | c.913C>T | p.Arg305Cys | missense_variant | 4/4 | 2 | |||
TUBA4A | ENST00000498660.1 | n.778C>T | non_coding_transcript_exon_variant | 3/3 | 3 | ||||
TUBA4A | ENST00000398989.2 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251488Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135916
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727246
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 22 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 22, 2014 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect on protein binding (Smith et al., 214; Ganne et al., 2023); This variant is associated with the following publications: (PMID: 26465396, 31585128, 31574570, 28412269, 25374358, 33378215, 34830115, 34169147, 36747013) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at