17-82929368-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005993.5(TBCD):c.2859T>C(p.Asp953=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,612,410 control chromosomes in the GnomAD database, including 50,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4698 hom., cov: 34)
  • Exomes 𝑓: 0.25 (46140 hom.)
• Consequence: TBCD NM_005993.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.54

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-82929368-T-C is Benign according to our data. Variant chr17-82929368-T-C is described in ClinVar as [Benign]. Clinvar id is 1167402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCD	NM_005993.5	c.2859T>C	p.Asp953=	synonymous_variant	32/39	ENST00000355528.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCD	ENST00000355528.9	c.2859T>C	p.Asp953=	synonymous_variant	32/39	1	NM_005993.5	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37819 AN: 152070 Hom.: 4693 Cov.: 34

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.256

GnomAD3 exomes AF: 0.253 AC: 62652 AN: 248076 Hom.: 8040 AF XY: 0.252 AC XY: 33987 AN XY: 134624

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.188

Gnomad SAS exome AF: 0.252

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.250 AC: 365007 AN: 1460220 Hom.: 46140 Cov.: 72 AF XY: 0.250 AC XY: 181425 AN XY: 726268

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.249 AC: 37839 AN: 152190 Hom.: 4698 Cov.: 34 AF XY: 0.250 AC XY: 18578 AN XY: 74388

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.254

Alfa AF: 0.244 Hom.: 6141

Bravo AF: 0.249

Asia WGS AF: 0.245 AC: 852 AN: 3478

EpiCase AF: 0.254

EpiControl AF: 0.261

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.025
Dann	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1127986; hg19: chr17-80887244; COSMIC: COSV62801180; COSMIC: COSV62801180;