rs61741669

Positions:

chr19-6496157-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006087.4(TUBB4A):c.342C>T(p.Asp114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00617 in 1,614,102 control chromosomes in the GnomAD database, including 541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 292 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 249 hom. )

Consequence

TUBB4A
NM_006087.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.999

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]

TUBB4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016824007).

BP6

Variant 19-6496157-G-A is Benign according to our data. Variant chr19-6496157-G-A is described in ClinVar as [Benign]. Clinvar id is 330265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-6496157-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.999 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB4A	NM_006087.4 linkuse as main transcript	c.342C>T	p.Asp114=	synonymous_variant	4/4	ENST00000264071.7	NP_006078.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB4A	ENST00000264071.7 linkuse as main transcript	c.342C>T	p.Asp114=	synonymous_variant	4/4	1	NM_006087.4	ENSP00000264071	P1

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5068

AN:

152102

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.00878

AC:

2208

AN:

251370

Hom.:

130

AF XY:

0.00636

AC XY:

864

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.00541

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00333

AC:

4875

AN:

1461882

Hom.:

249

Cov.:

AF XY:

0.00284

AC XY:

2062

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.00653

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.00740

GnomAD4 genome

AF:

0.0334

AC:

5083

AN:

152220

Hom.:

292

Cov.:

AF XY:

0.0325

AC XY:

2416

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0378

ESP6500AA

AF:

0.114

AC:

502

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0107

AC:

1304

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypomyelinating leukodystrophy 6

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Torsion dystonia 4

Benign:1

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.0

DANN

Benign

0.80

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.31

T;T

MetaRNN

Benign

0.0017

T;T

MutationTaster

Benign

1.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.23

GERP RS

-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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over