chr17-82752221-G-T

Position:

• chr17-82752221-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.28G>T​(p.Gly10Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,524,528 control chromosomes in the GnomAD database, including 14,468 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (997 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13471 hom.)
• Consequence: TBCD NM_005993.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.140

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014931858).
• BP6: Variant 17-82752221-G-T is Benign according to our data. Variant chr17-82752221-G-T is described in ClinVar as [Benign]. Clinvar id is 1167727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCD	NM_005993.5	c.28G>T	p.Gly10Cys	missense_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.28G>T	p.Gly10Cys	missense_variant	1/39	1	NM_005993.5	ENSP00000347719	P1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14724 AN: 152112 Hom.: 997 Cov.: 33

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0739

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.0993

GnomAD3 exomes AF: 0.134 AC: 15535 AN: 115536 Hom.: 1473 AF XY: 0.149 AC XY: 9547 AN XY: 63984

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.0461

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0768

Gnomad SAS exome AF: 0.271

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.133 AC: 182038 AN: 1372302 Hom.: 13471 Cov.: 31 AF XY: 0.138 AC XY: 93207 AN XY: 677094

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.0511

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.0776

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.0968 AC: 14733 AN: 152226 Hom.: 997 Cov.: 33 AF XY: 0.0990 AC XY: 7370 AN XY: 74424

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.0631

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0745

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.0992

Alfa AF: 0.121 Hom.: 419

Bravo AF: 0.0846

TwinsUK AF: 0.121 AC: 447

ALSPAC AF: 0.128 AC: 494

ESP6500AA AF: 0.0203 AC: 61

ESP6500EA AF: 0.100 AC: 657

ExAC AF: 0.0768 AC: 4668

Asia WGS AF: 0.179 AC: 620 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.32	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.68	N;.
REVEL	Benign	0.055
Sift	Uncertain	0.015	D;.
Sift4G	Benign	0.075	T;T
Polyphen		0.99	D;.
Vest4		0.10
MPC		1.0
ClinPred		0.026	T
GERP RS		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.15

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: rs11550062; hg19: chr17-80710097; COSMIC: COSV56181802; COSMIC: COSV56181802;