Genetic Variant NM_001355221.1:c.12+540_12+541delGG (chr2-219253950-CGG-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001355221.1(TUBA4B):c.12+540_12+541delGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000055 in 509,124 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000032 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

TUBA4B
NM_001355221.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.431

Variant links:

Genes affected

TUBA4B (HGNC:18637): (tubulin alpha 4b) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBA4B links:

TUBA4A (HGNC:12407): (tubulin alpha 4a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

TUBA4A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TUBA4B	NM_001355221.1 link	c.12+540_12+541delGG	intron_variant	Intron 1 of 3	ENST00000490341.3	NP_001342150.1
TUBA4A	NM_001278552.2 link	c.-43+143_-43+144delCC	intron_variant	Intron 1 of 3		NP_001265481.1	P68366-2
TUBA4A	XM_047445674.1 link	c.30+268_30+269delCC	intron_variant	Intron 1 of 3		XP_047301630.1
TUBA4A	NM_006000.3 link	c.-94_-93delCC	upstream_gene_variant		ENST00000248437.9	NP_005991.1	P68366-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA4B	ENST00000490341.3 link	c.12+532_12+533delGG		intron_variant	Intron 1 of 3	2	NM_001355221.1	ENSP00000487719.1		Q9H853
TUBA4A	ENST00000248437.9 link	c.-94_-93delCC		upstream_gene_variant		1	NM_006000.3	ENSP00000248437.4		P68366-1

Frequencies

GnomAD3 genomes

AF:

0.0000317

AC:

AN:

126366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000276

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000717

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:

0.0000627

AC:

AN:

382698

Hom.:

AF XY:

0.0000643

AC XY:

AN XY:

186650

show subpopulations

Gnomad4 AFR exome

AF:

0.000170

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000134

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.000315

Gnomad4 FIN exome

AF:

0.0000425

Gnomad4 NFE exome

AF:

0.0000416

Gnomad4 OTH exome

AF:

0.000168

GnomAD4 genome

AF:

0.0000316

AC:

AN:

126426

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

61470

show subpopulations

Gnomad4 AFR

AF:

0.0000276

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000720

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over