rs11078015

Variant names:

• chr17-82825133-T-C
• rs11078015
• NM_005993.5:c.1318+10199T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005993.5(TBCD):​c.1318+10199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,942 control chromosomes in the GnomAD database, including 16,065 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16065 hom., cov: 31)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCD	NM_005993.5	c.1318+10199T>C		intron_variant	Intron 13 of 38	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9	c.1318+10199T>C		intron_variant	Intron 13 of 38	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69510 AN: 151824 Hom.: 16032 Cov.: 31

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.458 AC: 69609 AN: 151942 Hom.: 16065 Cov.: 31 AF XY: 0.459 AC XY: 34085 AN XY: 74248

African (AFR) AF: 0.488 AC: 20225 AN: 41424

American (AMR) AF: 0.485 AC: 7413 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2776 AN: 5156

South Asian (SAS) AF: 0.351 AC: 1690 AN: 4812

European-Finnish (FIN) AF: 0.453 AC: 4781 AN: 10558

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29760 AN: 67942

Other (OTH) AF: 0.467 AC: 982 AN: 2104

Alfa AF: 0.446 Hom.: 40554

Bravo AF: 0.463

Asia WGS AF: 0.442 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.0
DANN	Benign	0.36
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11078015; hg19: chr17-80783009;