chr2-219253772-TC-T

Variant names:

• chr2-219253772-TC-T
• rs45617738
• NM_006000.3:c.3+83delG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006000.3(TUBA4A):​c.3+83delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,478,208 control chromosomes in the GnomAD database, including 61 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (29 hom.)
• Consequence: TUBA4A NM_006000.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.391

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-219253772-TC-T is Benign according to our data. Variant chr2-219253772-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 1186396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1595/151506) while in subpopulation AFR AF= 0.0358 (1476/41210). AF 95% confidence interval is 0.0343. There are 32 homozygotes in gnomad4. There are 751 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1595 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA4A	NM_006000.3	c.3+83delG		intron_variant	Intron 1 of 3	ENST00000248437.9	NP_005991.1
TUBA4B	NM_001355221.1	c.12+357delC		intron_variant	Intron 1 of 3	ENST00000490341.3	NP_001342150.1
TUBA4A	NM_001278552.2	c.-43+322delG		intron_variant	Intron 1 of 3		NP_001265481.1
TUBA4A	XM_047445674.1	c.30+447delG		intron_variant	Intron 1 of 3		XP_047301630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA4A	ENST00000248437.9	c.3+83delG		intron_variant	Intron 1 of 3	1	NM_006000.3	ENSP00000248437.4
TUBA4B	ENST00000490341.3	c.12+354delC		intron_variant	Intron 1 of 3	2	NM_001355221.1	ENSP00000487719.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1590 AN: 151390 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00440

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000545

Gnomad OTH AF: 0.00577

GnomAD4 exome AF: 0.00132 AC: 1748 AN: 1326702 Hom.: 29 AF XY: 0.00118 AC XY: 776 AN XY: 656828

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.000604

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000930

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000300

Gnomad4 OTH exome AF: 0.00283

GnomAD4 genome AF: 0.0105 AC: 1595 AN: 151506 Hom.: 32 Cov.: 32 AF XY: 0.0101 AC XY: 751 AN XY: 74014

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.00439

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000545

Gnomad4 OTH AF: 0.00571

Alfa AF: 0.00961 Hom.: 5

Bravo AF: 0.0123

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 16, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs45617738; hg19: chr2-220118494;