Variant 17-82752223-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005993.5(TBCD):c.30C>T(p.Gly10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,524,226 control chromosomes in the GnomAD database, including 377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 30 hom., cov: 33)

Exomes 𝑓: 0.021 ( 347 hom. )

Consequence

TBCD
NM_005993.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.200

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-82752223-C-T is Benign according to our data. Variant chr17-82752223-C-T is described in ClinVar as [Benign]. Clinvar id is 1570656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0152 (2311/152248) while in subpopulation EAS AF= 0.0272 (141/5176). AF 95% confidence interval is 0.0236. There are 30 homozygotes in gnomad4. There are 1158 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCD	NM_005993.5 linkuse as main transcript	c.30C>T	p.Gly10=	synonymous_variant	1/39	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9 linkuse as main transcript	c.30C>T	p.Gly10=	synonymous_variant	1/39	1	NM_005993.5	ENSP00000347719	P1	Q9BTW9-1

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2314

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.00620

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0164

AC:

1887

AN:

115256

Hom.:

AF XY:

0.0162

AC XY:

1037

AN XY:

63890

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00517

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.0310

Gnomad SAS exome

AF:

0.00665

Gnomad FIN exome

AF:

0.0352

Gnomad NFE exome

AF:

0.0212

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.0207

AC:

28434

AN:

1371978

Hom.:

347

Cov.:

AF XY:

0.0203

AC XY:

13722

AN XY:

676988

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.00576

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0450

Gnomad4 SAS exome

AF:

0.00644

Gnomad4 FIN exome

AF:

0.0336

Gnomad4 NFE exome

AF:

0.0218

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0152

AC:

2311

AN:

152248

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1158

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.0272

Gnomad4 SAS

AF:

0.00579

Gnomad4 FIN

AF:

0.0333

Gnomad4 NFE

AF:

0.0208

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0173

Hom.:

Bravo

AF:

0.0130

Asia WGS

AF:

0.0120

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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