rs1553500862

Positions:

• chr2-131478191-C-A
• chr2-131478191-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PP2 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

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

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity TBA3D_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TUBA3D. . Gene score misZ 1.5331 (greater than the threshold 3.09). Trascript score misZ 3.5821 (greater than threshold 3.09). GenCC has associacion of gene with keratoconus 9.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBA3D	ENST00000321253.7	c.31C>A	p.Gln11Lys	missense_variant	2/5	1	NM_080386.4	ENSP00000326042	P1
MZT2A	ENST00000427024.5	c.279-6009G>T		intron_variant, NMD_transcript_variant		3		ENSP00000403353
MZT2A	ENST00000445782.2	n.331-6009G>T		intron_variant, non_coding_transcript_variant		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
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
MutationTaster	Benign	1.0	D
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-132235764;