17-82905981-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005993.5(TBCD):ā€‹c.1850T>Gā€‹(p.Met617Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. M617T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

TBCD
NM_005993.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.106
Variant links:
Genes affected
TBCD (HGNC:11581): (tubulin folding cofactor D) Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12926033).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TBCDNM_005993.5 linkuse as main transcriptc.1850T>G p.Met617Arg missense_variant 20/39 ENST00000355528.9 NP_005984.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TBCDENST00000355528.9 linkuse as main transcriptc.1850T>G p.Met617Arg missense_variant 20/391 NM_005993.5 ENSP00000347719 P1Q9BTW9-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455964
Hom.:
0
Cov.:
44
AF XY:
0.00
AC XY:
0
AN XY:
724222
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
11
DANN
Benign
0.84
DEOGEN2
Benign
0.019
T;.;.;.;T;T;.;T;.;.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.39
T;T;T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.13
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.69
N;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.30
N;.;.;.;.;.;.;.;.;.;.
REVEL
Benign
0.19
Sift
Benign
0.14
T;.;.;.;.;.;.;.;.;.;.
Sift4G
Benign
0.30
T;T;T;T;T;T;D;T;D;D;D
Polyphen
0.019
B;.;.;.;.;.;.;.;.;.;.
Vest4
0.24
MutPred
0.43
Gain of solvent accessibility (P = 0.0105);Gain of solvent accessibility (P = 0.0105);.;.;.;.;.;.;.;.;.;
MVP
0.40
MPC
0.44
ClinPred
0.045
T
GERP RS
1.9
Varity_R
0.082
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs2292971; hg19: chr17-80863857; API