2-131480330-T-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_080386.4(TUBA3D):āc.637T>Cā(p.Cys213Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
TUBA3D
NM_080386.4 missense
NM_080386.4 missense
Scores
3
8
3
Clinical Significance
Conservation
PhyloP100: 5.27
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, TUBA3D
PP3
MetaRNN computational evidence supports a deleterious effect, 0.966
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBA3D | NM_080386.4 | c.637T>C | p.Cys213Arg | missense_variant | 4/5 | ENST00000321253.7 | |
MZT2A | XM_005263742.4 | c.320-8148A>G | intron_variant | ||||
MZT2A | XM_047445568.1 | c.623-8148A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA3D | ENST00000321253.7 | c.637T>C | p.Cys213Arg | missense_variant | 4/5 | 1 | NM_080386.4 | P1 | |
TUBA3D | ENST00000409047.2 | n.463T>C | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
MZT2A | ENST00000427024.5 | c.279-8148A>G | intron_variant, NMD_transcript_variant | 3 | |||||
MZT2A | ENST00000445782.2 | n.331-8148A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251168Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461586Hom.: 0 Cov.: 73 AF XY: 0.00 AC XY: 0AN XY: 727104
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GnomAD4 genome Cov.: 31
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2023 | The c.637T>C (p.C213R) alteration is located in exon 1 (coding exon 1) of the TUBA3D gene. This alteration results from a T to C substitution at nucleotide position 637, causing the cysteine (C) at amino acid position 213 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift4G
Uncertain
D
Vest4
MutPred
Gain of disorder (P = 0.051);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at