17-82752160-CG-C

Position:

• chr17-82752160-CG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005993.5(TBCD):​c.-33del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,486,094 control chromosomes in the GnomAD database, including 541 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (101 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (440 hom.)
• Consequence: TBCD NM_005993.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.537

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-82752160-CG-C is Benign according to our data. Variant chr17-82752160-CG-C is described in ClinVar as [Benign]. Clinvar id is 1259319.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCD	NM_005993.5	c.-33del		5_prime_UTR_variant	1/39	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9	c.-33del		5_prime_UTR_variant	1/39	1	NM_005993.5	ENSP00000347719	P1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1788 AN: 152174 Hom.: 97 Cov.: 33

Gnomad AFR AF: 0.00248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.0364 AC: 3031 AN: 83370 Hom.: 309 AF XY: 0.0268 AC XY: 1266 AN XY: 47214

Gnomad AFR exome AF: 0.00411

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00564

Gnomad FIN exome AF: 0.00215

Gnomad NFE exome AF: 0.00223

Gnomad OTH exome AF: 0.0185

GnomAD4 exome AF: 0.00572 AC: 7631 AN: 1333808 Hom.: 440 Cov.: 30 AF XY: 0.00542 AC XY: 3561 AN XY: 657458

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000343

Gnomad4 SAS exome AF: 0.00570

Gnomad4 FIN exome AF: 0.00177

Gnomad4 NFE exome AF: 0.00231

Gnomad4 OTH exome AF: 0.00695

GnomAD4 genome AF: 0.0118 AC: 1798 AN: 152286 Hom.: 101 Cov.: 33 AF XY: 0.0130 AC XY: 966 AN XY: 74464

Gnomad4 AFR AF: 0.00248

Gnomad4 AMR AF: 0.0984

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00118 Hom.: 1

Bravo AF: 0.0206

Asia WGS AF: 0.00664 AC: 23 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 21, 2021

- -

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: rs34420503; hg19: chr17-80710036;