NM_001355221.1:c.12+540_12+541dupGG

Variant names:

• chr2-219253950-C-CGG
• rs3051654
• NM_001355221.1:c.12+540_12+541dupGG

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+541dupGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 509,066 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 0.00030 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000091 (0 hom.)
• Consequence: TUBA4B NM_001355221.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA4B	ENST00000490341.3	c.12+531_12+532insGG		intron_variant	Intron 1 of 3	2	NM_001355221.1	ENSP00000487719.1
TUBA4A	ENST00000248437.9	c.-93_-92insCC		upstream_gene_variant		1	NM_006000.3	ENSP00000248437.4

Frequencies

GnomAD3 genomes AF: 0.000301 AC: 38 AN: 126356 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000498

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000239

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000233

Gnomad OTH AF: 0.000588

GnomAD4 exome AF: 0.0000915 AC: 35 AN: 382710 Hom.: 0 Cov.: 12 AF XY: 0.0000964 AC XY: 18 AN XY: 186674

Gnomad4 AFR exome AF: 0.000340

Gnomad4 AMR exome AF: 0.000557

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000425

Gnomad4 NFE exome AF: 0.0000867

Gnomad4 OTH exome AF: 0.000112

GnomAD4 genome AF: 0.000301 AC: 38 AN: 126356 Hom.: 0 Cov.: 30 AF XY: 0.000342 AC XY: 21 AN XY: 61392

Gnomad4 AFR AF: 0.000498

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000239

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000233

Gnomad4 OTH AF: 0.000588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3051654; hg19: chr2-220118672;