chr2-219251056-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_006000.3(TUBA4A):c.643C>T(p.Arg215Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,894 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 Uncertain significance (★).
Frequency
Consequence
NM_006000.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBA4A | NM_006000.3 | c.643C>T | p.Arg215Cys | missense_variant | Exon 4 of 4 | ENST00000248437.9 | NP_005991.1 | |
TUBA4A | NM_001278552.2 | c.598C>T | p.Arg200Cys | missense_variant | Exon 4 of 4 | NP_001265481.1 | ||
TUBA4A | XM_047445674.1 | c.670C>T | p.Arg224Cys | missense_variant | Exon 4 of 4 | XP_047301630.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBA4A | ENST00000248437.9 | c.643C>T | p.Arg215Cys | missense_variant | Exon 4 of 4 | 1 | NM_006000.3 | ENSP00000248437.4 | ||
TUBA4A | ENST00000392088.6 | c.598C>T | p.Arg200Cys | missense_variant | Exon 4 of 4 | 2 | ENSP00000375938.2 | |||
TUBA4A | ENST00000398989.2 | c.184C>T | p.Arg62Cys | missense_variant | Exon 2 of 2 | 3 | ENSP00000396212.1 | |||
TUBA4A | ENST00000498660.1 | n.463C>T | non_coding_transcript_exon_variant | Exon 3 of 3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251496Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135922
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis 22 with frontotemporal dementia Pathogenic:1
- -
not provided Uncertain:1
Identified in an individual with familial amyotrophic lateral sclerosis with frontotemporal dementia; segregation testing was not performed (Smith BN et al., 2014); Published functional studies found this variant is associated with a small migration difference and altered incorporation into microtubules. However, alpha and beta tubulin dimer assembly was not significantly reduced; the significance of these functional differences is unclear (Smith BN et al., 2014); 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: 37024973, 25374358, 26934450, 27538057, 26780671, 35714755, 33027950, 34169147, 36943622, 36747013) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at