rs150812047

Variant names:

• chr19-6501375-C-A
• rs150812047
• NM_006087.4:c.189G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6501375-C-A
• chr19-6501375-C-G
• chr19-6501375-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001289130.2(TUBB4A):​c.-28G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBB4A NM_001289130.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.557
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hypomyelinating leukodystrophy 6

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Illumina
• TUBB4A-related neurologic disorder

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
• torsion dystonia 4

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06613529).
• BP6: Variant 19-6501375-C-A is Benign according to our data. Variant chr19-6501375-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2738501.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289130.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB4A	NM_006087.4	MANE Select	c.189G>T	p.Ala63Ala	synonymous	Exon 3 of 4	NP_006078.2
	TUBB4A	NM_001289130.2		c.-28G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_001276059.1	M0R1I1
	TUBB4A	NM_001289131.2		c.-28G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_001276060.1	M0R1I1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB4A	ENST00000264071.7	TSL:1 MANE Select	c.189G>T	p.Ala63Ala	synonymous	Exon 3 of 4	ENSP00000264071.1	P04350
	TUBB4A	ENST00000596291.2	TSL:2	c.-28G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000471880.2	M0R1I1
	TUBB4A	ENST00000714086.1		c.214G>T	p.Gly72Cys	missense	Exon 3 of 4	ENSP00000519377.1	A0AAQ5BHG7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hypomyelinating leukodystrophy 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.44
DANN	Benign	0.87
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.066	T
PhyloP100		-0.56
Sift4G	Benign	0.69	T
Vest4		0.25
MVP		0.59
GERP RS		-7.7
PromoterAI		0.0052	Neutral
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs150812047; hg19: chr19-6501386;