17-82796696-T-C

Variant names:

• chr17-82796696-T-C
• rs635996
• NM_005993.5:c.772-1061T>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.772-1061T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,132 control chromosomes in the GnomAD database, including 12,868 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 0.41 (12868 hom., cov: 33)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCD	NM_005993.5	c.772-1061T>C		intron_variant	Intron 7 of 38	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9	c.772-1061T>C		intron_variant	Intron 7 of 38	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62376 AN: 152014 Hom.: 12874 Cov.: 33

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.410 AC: 62382 AN: 152132 Hom.: 12868 Cov.: 33 AF XY: 0.408 AC XY: 30346 AN XY: 74386

African (AFR) AF: 0.426 AC: 17677 AN: 41494

American (AMR) AF: 0.422 AC: 6455 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1320 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2058 AN: 5180

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4822

European-Finnish (FIN) AF: 0.410 AC: 4341 AN: 10580

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27507 AN: 67974

Other (OTH) AF: 0.401 AC: 848 AN: 2114

Alfa AF: 0.383 Hom.: 1453

Bravo AF: 0.414

Asia WGS AF: 0.368 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.90
DANN	Benign	0.47
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs635996; hg19: chr17-80754572;