chr2-131478191-C-A

Variant names:

• chr2-131478191-C-A
• rs1553500862
• NM_080386.4:c.31C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_080386.4(TUBA3D):​c.31C>A​(p.Gln11Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TUBA3D NM_080386.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.97
• Publications: 0 publications found

Genes affected

TUBA3D (HGNC:24071): (tubulin alpha 3d) This gene encodes a member of the alpha tubulin family. Tubulin is a major component of microtubules, which are composed of alpha- and beta-tubulin heterodimers and microtubule-associated proteins in the cytoskeleton. Microtubules maintain cellular structure, function in intracellular transport, and play a role in spindle formation during mitosis. [provided by RefSeq, Oct 2011]

MZT2A (HGNC:33187): (mitotic spindle organizing protein 2A) Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity TBA3D_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA3D	NM_080386.4	c.31C>A	p.Gln11Lys	missense_variant	Exon 2 of 5	ENST00000321253.7	NP_525125.2
MZT2A	XM_047445568.1	c.623-6009G>T		intron_variant	Intron 1 of 2		XP_047301524.1
MZT2A	XM_005263742.4	c.320-6009G>T		intron_variant	Intron 2 of 3		XP_005263799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA3D	ENST00000321253.7	c.31C>A	p.Gln11Lys	missense_variant	Exon 2 of 5	1	NM_080386.4	ENSP00000326042.6
MZT2A	ENST00000427024.5	n.278-6009G>T		intron_variant	Intron 2 of 4	3		ENSP00000403353.1
MZT2A	ENST00000445782.2	n.331-6009G>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Benign	0.97
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.50	D
PhyloP100		7.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.1	N
REVEL	Pathogenic	0.68
Sift4G	Uncertain	0.0030	D
Vest4		0.89
MutPred		0.79		Gain of methylation at Q11 (P = 0.0228);
MVP		0.64
ClinPred		0.99	D
GERP RS		2.5
Varity_R		0.11
gMVP		0.79
Mutation Taster		=83/17	polymorphism

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: rs1553500862; hg19: chr2-132235764;