GeneBe

rs756938019

Positions:

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_080386.4(TUBA3D):​c.201del​(p.Phe67LeufsTer26) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

TUBA3D
NM_080386.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.37
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TUBA3DNM_080386.4 linkuse as main transcriptc.201del p.Phe67LeufsTer26 frameshift_variant 2/5 ENST00000321253.7 NP_525125.2
MZT2AXM_005263742.4 linkuse as main transcriptc.320-6177del intron_variant XP_005263799.2
MZT2AXM_047445568.1 linkuse as main transcriptc.623-6177del intron_variant XP_047301524.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TUBA3DENST00000321253.7 linkuse as main transcriptc.201del p.Phe67LeufsTer26 frameshift_variant 2/51 NM_080386.4 ENSP00000326042 P1
MZT2AENST00000427024.5 linkuse as main transcriptc.279-6177del intron_variant, NMD_transcript_variant 3 ENSP00000403353
MZT2AENST00000445782.2 linkuse as main transcriptn.331-6177del 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

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs756938019; hg19: chr2-132235931; API