chr17-82757178-T-C

Variant names:

• chr17-82757178-T-C
• rs2451214
• NM_005993.5:c.235+963T>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.235+963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,058 control chromosomes in the GnomAD database, including 29,556 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 0.62 (29556 hom., cov: 32)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.69
• Publications: 13 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCD	NM_005993.5	c.235+963T>C		intron_variant	Intron 2 of 38	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9	c.235+963T>C		intron_variant	Intron 2 of 38	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94573 AN: 151938 Hom.: 29499 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.623 AC: 94691 AN: 152058 Hom.: 29556 Cov.: 32 AF XY: 0.623 AC XY: 46333 AN XY: 74338

African (AFR) AF: 0.654 AC: 27134 AN: 41476

American (AMR) AF: 0.592 AC: 9042 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2170 AN: 3466

East Asian (EAS) AF: 0.604 AC: 3118 AN: 5166

South Asian (SAS) AF: 0.641 AC: 3090 AN: 4818

European-Finnish (FIN) AF: 0.608 AC: 6422 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41638 AN: 67974

Other (OTH) AF: 0.625 AC: 1320 AN: 2112

Alfa AF: 0.629 Hom.: 5941

Bravo AF: 0.620

Asia WGS AF: 0.638 AC: 2219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.48
DANN	Benign	0.69
PhyloP100		-3.7
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: rs2451214; hg19: chr17-80715054;