chr17-82829419-T-TA

Position:

• chr17-82829419-T-TA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005993.5(TBCD):​c.1318+14486dup variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10205 hom., cov: 0)
  • Exomes 𝑓: 0.37 (153 hom.)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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]

ZNF750 (HGNC:25843): (zinc finger protein 750) This gene encodes a protein with a nuclear localization site and a C2H2 zinc finger domain. Mutations in this gene have been associated with seborrhea-like dermatitis with psoriasiform elements. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCD	NM_005993.5	c.1318+14486dup		intron_variant		ENST00000355528.9
ZNF750	NM_024702.3			downstream_gene_variant		ENST00000269394.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCD	ENST00000355528.9	c.1318+14486dup		intron_variant		1	NM_005993.5	P1
ZNF750	ENST00000269394.4			downstream_gene_variant		1	NM_024702.3	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54838 AN: 152104 Hom.: 10205 Cov.: 0

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.368 AC: 836 AN: 2272 Hom.: 153 Cov.: 0 AF XY: 0.369 AC XY: 424 AN XY: 1150

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.360 AC: 54849 AN: 152224 Hom.: 10205 Cov.: 0 AF XY: 0.359 AC XY: 26753 AN XY: 74418

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.368

Alfa AF: 0.153 Hom.: 281

Bravo AF: 0.359

Asia WGS AF: 0.360 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs35156590; hg19: chr17-80787295;