chr19-6495111-C-T

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.275
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 -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
TUBB4ANM_006087.4 linkuse as main transcriptc.*53G>A 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.*53G>A 3_prime_UTR_variant 4/41 NM_006087.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0133
AC:
2016
AN:
151932
Hom.:
44
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0463
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00459
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00959
GnomAD4 exome
AF:
0.00129
AC:
1857
AN:
1442136
Hom.:
37
Cov.:
31
AF XY:
0.00108
AC XY:
774
AN XY:
715616
show subpopulations
Gnomad4 AFR exome
AF:
0.0471
Gnomad4 AMR exome
AF:
0.00190
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000507
Gnomad4 SAS exome
AF:
0.0000836
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000691
Gnomad4 OTH exome
AF:
0.00218
GnomAD4 genome
AF:
0.0133
AC:
2020
AN:
152048
Hom.:
44
Cov.:
32
AF XY:
0.0125
AC XY:
929
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0463
Gnomad4 AMR
AF:
0.00458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00949
Alfa
AF:
0.00180
Hom.:
1
Bravo
AF:
0.0154
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

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 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 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 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.6
DANN
Benign
0.48

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: rs113953942; hg19: chr19-6495122; API