rs564748070

Variant names:

• chr19-6495095-G-A
• rs564748070
• NM_006087.4:c.*69C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6495095-G-A
• chr19-6495095-G-C
• chr19-6495095-G-T

Variant summary

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

The NM_006087.4(TUBB4A):​c.*69C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,573,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TUBB4A NM_006087.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.920
• 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

ENSG00000268191 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006087.4. 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.*69C>T		3_prime_UTR	Exon 4 of 4	NP_006078.2
	TUBB4A	NM_001289123.2		c.*69C>T		3_prime_UTR	Exon 5 of 5	NP_001276052.1	M0QZL7
	TUBB4A	NM_001289127.2		c.*69C>T		3_prime_UTR	Exon 5 of 5	NP_001276056.1	M0R278

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB4A	ENST00000264071.7	TSL:1 MANE Select	c.*69C>T		3_prime_UTR	Exon 4 of 4	ENSP00000264071.1	P04350
	TUBB4A	ENST00000714086.1		c.*943C>T		3_prime_UTR	Exon 4 of 4	ENSP00000519377.1	A0AAQ5BHG7
	TUBB4A	ENST00000598635.2	TSL:4	c.*69C>T		downstream_gene	N/A	ENSP00000470627.2	M0QZL7

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1421498 Hom.: 0 Cov.: 29 AF XY: 0.00000142 AC XY: 1 AN XY: 704406

African (AFR) AF: 0.00 AC: 0 AN: 32622

American (AMR) AF: 0.00 AC: 0 AN: 42404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24136

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39220

South Asian (SAS) AF: 0.00 AC: 0 AN: 81206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086366

Other (OTH) AF: 0.00 AC: 0 AN: 58764

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152030 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74258

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.85
PhyloP100		0.92

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: rs564748070; hg19: chr19-6495106;