chr19-6495111-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_006087.4(TUBB4A):c.*53G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,594,184 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.013 ( 44 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 37 hom. )
Consequence
TUBB4A
NM_006087.4 3_prime_UTR
NM_006087.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.275
Genes affected
TUBB4A (HGNC:20774): (tubulin beta 4A class IVa) This gene encodes a member of the beta tubulin family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene cause hypomyelinating leukodystrophy-6 and autosomal dominant torsion dystonia-4. Alternate splicing results in multiple transcript variants encoding different isoforms. A pseudogene of this gene is found on chromosome X. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 19-6495111-C-T is Benign according to our data. Variant chr19-6495111-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 330259.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2020/152048) while in subpopulation AFR AF= 0.0463 (1919/41452). AF 95% confidence interval is 0.0446. There are 44 homozygotes in gnomad4. There are 929 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2020 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB4A | NM_006087.4 | c.*53G>A | 3_prime_UTR_variant | 4/4 | ENST00000264071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB4A | ENST00000264071.7 | c.*53G>A | 3_prime_UTR_variant | 4/4 | 1 | NM_006087.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0133 AC: 2016AN: 151932Hom.: 44 Cov.: 32
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GnomAD4 exome AF: 0.00129 AC: 1857AN: 1442136Hom.: 37 Cov.: 31 AF XY: 0.00108 AC XY: 774AN XY: 715616
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GnomAD4 genome AF: 0.0133 AC: 2020AN: 152048Hom.: 44 Cov.: 32 AF XY: 0.0125 AC XY: 929AN XY: 74332
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Torsion dystonia 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Hypomyelinating leukodystrophy 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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