2-131480123-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 7P and 4B. PM1PP2PP3_StrongBS2
The NM_080386.4(TUBA3D):c.430G>A(p.Gly144Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,730 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
TUBA3D
NM_080386.4 missense
NM_080386.4 missense
Scores
5
7
2
Clinical Significance
Conservation
PhyloP100: 8.39
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 Uncertain_significance. Variant got 3 ACMG points.
PM1
In a binding_site (size 0) in uniprot entity TBA3D_HUMAN
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, 0.957
BS2
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBA3D | NM_080386.4 | c.430G>A | p.Gly144Ser | missense_variant | 4/5 | ENST00000321253.7 | NP_525125.2 | |
MZT2A | XM_005263742.4 | c.320-7941C>T | intron_variant | XP_005263799.2 | ||||
MZT2A | XM_047445568.1 | c.623-7941C>T | intron_variant | XP_047301524.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBA3D | ENST00000321253.7 | c.430G>A | p.Gly144Ser | missense_variant | 4/5 | 1 | NM_080386.4 | ENSP00000326042 | P1 | |
TUBA3D | ENST00000409047.2 | n.256G>A | non_coding_transcript_exon_variant | 3/3 | 2 | |||||
MZT2A | ENST00000427024.5 | c.279-7941C>T | intron_variant, NMD_transcript_variant | 3 | ENSP00000403353 | |||||
MZT2A | ENST00000445782.2 | n.331-7941C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151892Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000809 AC: 2AN: 247284Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133670
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460838Hom.: 0 Cov.: 63 AF XY: 0.00000688 AC XY: 5AN XY: 726686
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151892Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74174
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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 | Jun 24, 2022 | The c.430G>A (p.G144S) alteration is located in exon 1 (coding exon 1) of the TUBA3D gene. This alteration results from a G to A substitution at nucleotide position 430, causing the glycine (G) at amino acid position 144 to be replaced by a serine (S). 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
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift4G
Uncertain
D
Vest4
MutPred
Gain of glycosylation at G144 (P = 0.0747);
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