2-219250442-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_006000.3(TUBA4A):c.1257C>T(p.Ser419=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
TUBA4A
NM_006000.3 synonymous
NM_006000.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.42
Genes affected
TUBA4A (HGNC:12407): (tubulin alpha 4a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 2-219250442-G-A is Benign according to our data. Variant chr2-219250442-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.42 with no splicing effect.
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBA4A | NM_006000.3 | c.1257C>T | p.Ser419= | synonymous_variant | 4/4 | ENST00000248437.9 | |
TUBA4A | NM_001278552.2 | c.1212C>T | p.Ser404= | synonymous_variant | 4/4 | ||
TUBA4A | XM_047445674.1 | c.1284C>T | p.Ser428= | synonymous_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA4A | ENST00000248437.9 | c.1257C>T | p.Ser419= | synonymous_variant | 4/4 | 1 | NM_006000.3 | P1 | |
TUBA4A | ENST00000392088.6 | c.1212C>T | p.Ser404= | synonymous_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251476Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135910
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727246
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74426
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | TUBA4A: BP4, BP7 - |
TUBA4A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 03, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at