rs1292053

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016261.4(TUBD1):​c.227T>G​(p.Met76Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M76T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

TUBD1
NM_016261.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.26
Variant links:
Genes affected
TUBD1 (HGNC:16811): (tubulin delta 1) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization; mitotic cell cycle; and positive regulation of smoothened signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30910176).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUBD1NM_016261.4 linkc.227T>G p.Met76Arg missense_variant Exon 3 of 9 ENST00000325752.8 NP_057345.2 Q9UJT1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUBD1ENST00000325752.8 linkc.227T>G p.Met76Arg missense_variant Exon 3 of 9 5 NM_016261.4 ENSP00000320797.3 Q9UJT1-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
44
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Benign
-0.038
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.028
.;T;.;.;.;T;T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.67
T;T;T;T;.;.;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.31
T;T;T;T;T;T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
0.81
L;L;L;L;L;L;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.32
.;N;N;N;N;.;.
REVEL
Benign
0.16
Sift
Uncertain
0.0060
.;D;D;D;D;.;.
Sift4G
Uncertain
0.032
D;D;D;D;D;D;.
Polyphen
0.037, 0.0080
.;B;B;.;.;B;.
Vest4
0.36
MutPred
0.80
Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);.;
MVP
0.74
MPC
0.21
ClinPred
0.54
D
GERP RS
4.1
Varity_R
0.46
gMVP
0.60

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: chr17-57963537; API