rs3744161

chr17-82870181-G-Achr17-82870181-G-Cchr17-82870181-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005993.5(TBCD):c.1319-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,609,494 control chromosomes in the GnomAD database, including 258,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21529 hom., cov: 33)
  • Exomes 𝑓: 0.57 (237002 hom.)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.484

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]

LOC124904096 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-82870181-G-A is Benign according to our data. Variant chr17-82870181-G-A is described in ClinVar as [Benign]. Clinvar id is 1265397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCD	NM_005993.5	c.1319-43G>A		intron_variant		ENST00000355528.9
LOC124904096	XR_007065971.1	n.2446C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCD	ENST00000355528.9	c.1319-43G>A		intron_variant		1	NM_005993.5	P1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79274 AN: 151930 Hom.: 21511 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.535

GnomAD3 exomes AF: 0.563 AC: 137718 AN: 244402 Hom.: 39715 AF XY: 0.558 AC XY: 74335 AN XY: 133232

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.727

Gnomad SAS exome AF: 0.463

Gnomad FIN exome AF: 0.595

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.567 AC: 826919 AN: 1457446 Hom.: 237002 Cov.: 40 AF XY: 0.565 AC XY: 409692 AN XY: 725248

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.575

Gnomad4 OTH exome AF: 0.552

GnomAD4 genome AF: 0.522 AC: 79335 AN: 152048 Hom.: 21529 Cov.: 33 AF XY: 0.524 AC XY: 38975 AN XY: 74324

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.539

Alfa AF: 0.484 Hom.: 2648

Bravo AF: 0.516

Asia WGS AF: 0.542 AC: 1887 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3744161; hg19: chr17-80828057; COSMIC: COSV62801426;