NM_006000.3:c.1077T>A

Variant names:

• chr2-219250622-A-T
• rs1574883829
• NM_006000.3:c.1077T>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006000.3(TUBA4A):​c.1077T>A​(p.Pro359Pro) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBA4A NM_006000.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.91

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-6.91 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA4A	NM_006000.3	c.1077T>A	p.Pro359Pro	synonymous_variant	Exon 4 of 4	ENST00000248437.9	NP_005991.1
TUBA4A	NM_001278552.2	c.1032T>A	p.Pro344Pro	synonymous_variant	Exon 4 of 4		NP_001265481.1
TUBA4A	XM_047445674.1	c.1104T>A	p.Pro368Pro	synonymous_variant	Exon 4 of 4		XP_047301630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA4A	ENST00000248437.9	c.1077T>A	p.Pro359Pro	synonymous_variant	Exon 4 of 4	1	NM_006000.3	ENSP00000248437.4
TUBA4A	ENST00000392088.6	c.1032T>A	p.Pro344Pro	synonymous_variant	Exon 4 of 4	2		ENSP00000375938.2
TUBA4A	ENST00000398989.2	c.*150T>A		downstream_gene_variant		3		ENSP00000396212.1
TUBA4A	ENST00000498660.1	n.*107T>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.058
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs1574883829; hg19: chr2-220115344; COSMIC: COSV50280936; COSMIC: COSV50280936;