19-6495068-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006087.4(TUBB4A):​c.*96C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 1,453,870 control chromosomes in the GnomAD database, including 3,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 411 hom., cov: 32)
Exomes 𝑓: 0.053 ( 2708 hom. )

Consequence

TUBB4A
NM_006087.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0210
Variant links:
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 19-6495068-G-C is Benign according to our data. Variant chr19-6495068-G-C is described in ClinVar as [Benign]. Clinvar id is 330258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TUBB4ANM_006087.4 linkuse as main transcriptc.*96C>G 3_prime_UTR_variant 4/4 ENST00000264071.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TUBB4AENST00000264071.7 linkuse as main transcriptc.*96C>G 3_prime_UTR_variant 4/41 NM_006087.4 P1
ENST00000596027.1 linkuse as main transcript downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0645
AC:
9784
AN:
151712
Hom.:
411
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0751
Gnomad AMI
AF:
0.0648
Gnomad AMR
AF:
0.0503
Gnomad ASJ
AF:
0.0875
Gnomad EAS
AF:
0.213
Gnomad SAS
AF:
0.113
Gnomad FIN
AF:
0.0614
Gnomad MID
AF:
0.108
Gnomad NFE
AF:
0.0454
Gnomad OTH
AF:
0.0754
GnomAD4 exome
AF:
0.0525
AC:
68407
AN:
1302040
Hom.:
2708
Cov.:
21
AF XY:
0.0548
AC XY:
35300
AN XY:
644350
show subpopulations
Gnomad4 AFR exome
AF:
0.0779
Gnomad4 AMR exome
AF:
0.0564
Gnomad4 ASJ exome
AF:
0.0852
Gnomad4 EAS exome
AF:
0.201
Gnomad4 SAS exome
AF:
0.114
Gnomad4 FIN exome
AF:
0.0612
Gnomad4 NFE exome
AF:
0.0400
Gnomad4 OTH exome
AF:
0.0597
GnomAD4 genome
AF:
0.0644
AC:
9777
AN:
151830
Hom.:
411
Cov.:
32
AF XY:
0.0664
AC XY:
4925
AN XY:
74194
show subpopulations
Gnomad4 AFR
AF:
0.0748
Gnomad4 AMR
AF:
0.0504
Gnomad4 ASJ
AF:
0.0875
Gnomad4 EAS
AF:
0.212
Gnomad4 SAS
AF:
0.113
Gnomad4 FIN
AF:
0.0614
Gnomad4 NFE
AF:
0.0454
Gnomad4 OTH
AF:
0.0756
Alfa
AF:
0.0573
Hom.:
40
Bravo
AF:
0.0634
Asia WGS
AF:
0.130
AC:
450
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJul 06, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Torsion dystonia 4 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Hypomyelinating leukodystrophy 6 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.1
DANN
Benign
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs449824; hg19: chr19-6495079; API