17-82905981-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005993.5(TBCD):c.1850T>C(p.Met617Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,607,640 control chromosomes in the GnomAD database, including 157,642 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.48 ( 18827 hom., cov: 34)

Exomes 𝑓: 0.43 ( 138815 hom. )

Consequence

TBCD
NM_005993.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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]

TBCD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.391527E-6).

BP6

Variant 17-82905981-T-C is Benign according to our data. Variant chr17-82905981-T-C is described in ClinVar as [Benign]. Clinvar id is 1167401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCD	NM_005993.5 link	c.1850T>C	p.Met617Thr	missense_variant	Exon 20 of 39	ENST00000355528.9	NP_005984.3	Q9BTW9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9 link	c.1850T>C	p.Met617Thr	missense_variant	Exon 20 of 39	1	NM_005993.5	ENSP00000347719.4		Q9BTW9-1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73650

AN:

151994

Hom.:

18812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.656

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.438

AC:

107922

AN:

246480

Hom.:

24511

AF XY:

0.443

AC XY:

59237

AN XY:

133698

show subpopulations

Gnomad AFR exome

AF:

0.662

Gnomad AMR exome

AF:

0.373

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.270

Gnomad SAS exome

AF:

0.538

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.427

Gnomad OTH exome

AF:

0.446

GnomAD4 exome

AF:

0.433

AC:

629770

AN:

1455528

Hom.:

138815

Cov.:

AF XY:

0.435

AC XY:

315065

AN XY:

723978

show subpopulations

Gnomad4 AFR exome

AF:

0.667

Gnomad4 AMR exome

AF:

0.383

Gnomad4 ASJ exome

AF:

0.484

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.536

Gnomad4 FIN exome

AF:

0.416

Gnomad4 NFE exome

AF:

0.424

Gnomad4 OTH exome

AF:

0.448

GnomAD4 genome

AF:

0.485

AC:

73705

AN:

152112

Hom.:

18827

Cov.:

AF XY:

0.482

AC XY:

35822

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.656

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.488

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.537

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.422

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.429

Hom.:

30701

Bravo

AF:

0.491

TwinsUK

AF:

0.426

AC:

1579

ALSPAC

AF:

0.423

AC:

1630

ESP6500AA

AF:

0.674

AC:

2857

ESP6500EA

AF:

0.431

AC:

3645

ExAC

AF:

0.447

AC:

54064

Asia WGS

AF:

0.448

AC:

1555

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 06, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.13

DANN

Benign

0.21

DEOGEN2

Benign

0.014

T;.;.;.;T;T;.;T;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.023

T;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0000044

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.3

N;.;.;.;.;.;.;.;.;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

2.8

N;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.094

Sift

Benign

1.0

T;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.;.;.;.;.;.

Vest4

0.10

MPC

0.33

ClinPred

0.0024

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.15

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over