chr12-49185019-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_006009.4(TUBA1A):c.1347G>A(p.Glu449=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,934 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: 0.000042 ( 0 hom. )
Consequence
TUBA1A
NM_006009.4 synonymous
NM_006009.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.37
Genes affected
TUBA1A (HGNC:20766): (tubulin alpha 1a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulins. The genes encoding these microtubule constituents belong to 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, which are highly conserved among species. This gene encodes alpha tubulin and is highly similar to the mouse and rat Tuba1 genes. Northern blot studies have shown that the gene expression is predominantly found in morphologically differentiated neurologic cells. This gene is one of three alpha-tubulin genes in a cluster on chromosome 12q. Mutations in this gene cause lissencephaly type 3 (LIS3) - a neurological condition characterized by microcephaly, intellectual disability, and early-onset epilepsy caused by defective neuronal migration. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 12-49185019-C-T is Benign according to our data. Variant chr12-49185019-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1561411.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.37 with no splicing effect.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.1347G>A | p.Glu449= | synonymous_variant | 4/4 | ENST00000301071.12 | |
TUBA1A | NM_001270399.2 | c.1347G>A | p.Glu449= | synonymous_variant | 4/4 | ||
TUBA1A | NM_001270400.2 | c.1242G>A | p.Glu414= | synonymous_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA1A | ENST00000301071.12 | c.1347G>A | p.Glu449= | synonymous_variant | 4/4 | 1 | NM_006009.4 | P1 | |
TUBA1B-AS1 | ENST00000656133.1 | n.474-3264C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251462Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135906
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461798Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 727204
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at