17-82818167-C-T

Variant names:

• chr17-82818167-C-T
• rs662669
• NM_005993.5:c.1318+3233C>T

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+3233C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,084 control chromosomes in the GnomAD database, including 23,597 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 0.56 (23597 hom., cov: 33)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCD	NM_005993.5	c.1318+3233C>T		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+3233C>T		intron_variant	Intron 13 of 38	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84448 AN: 151966 Hom.: 23573 Cov.: 33

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.556 AC: 84510 AN: 152084 Hom.: 23597 Cov.: 33 AF XY: 0.555 AC XY: 41270 AN XY: 74358

African (AFR) AF: 0.571 AC: 23700 AN: 41478

American (AMR) AF: 0.523 AC: 7992 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2062 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2378 AN: 5168

South Asian (SAS) AF: 0.648 AC: 3126 AN: 4824

European-Finnish (FIN) AF: 0.546 AC: 5773 AN: 10570

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37714 AN: 67978

Other (OTH) AF: 0.537 AC: 1131 AN: 2106

Alfa AF: 0.447 Hom.: 1949

Bravo AF: 0.552

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.59
DANN	Benign	0.52
PhyloP100		-0.37
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: rs662669; hg19: chr17-80776043;