rs11550067

Variant names:

• chr17-82752223-C-T
• rs11550067
• NM_005993.5:c.30C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005993.5(TBCD):​c.30C>T​(p.Gly10Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,524,226 control chromosomes in the GnomAD database, including 377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (30 hom., cov: 33)
  • Exomes 𝑓: 0.021 (347 hom.)
• Consequence: TBCD NM_005993.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.200
• Publications: 3 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: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 17-82752223-C-T is Benign according to our data. Variant chr17-82752223-C-T is described in ClinVar as Benign. ClinVar VariationId is 1570656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.2 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0152 (2311/152248) while in subpopulation EAS AF = 0.0272 (141/5176). AF 95% confidence interval is 0.0236. There are 30 homozygotes in GnomAd4. There are 1158 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005993.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCD	NM_005993.5	MANE Select	c.30C>T	p.Gly10Gly	synonymous	Exon 1 of 39	NP_005984.3
	TBCD	NM_001411101.1		c.30C>T	p.Gly10Gly	synonymous	Exon 1 of 38	NP_001398030.1	A0A804HLI2
	TBCD	NM_001411102.1		c.30C>T	p.Gly10Gly	synonymous	Exon 1 of 38	NP_001398031.1	A0A804HJ32

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCD	ENST00000355528.9	TSL:1 MANE Select	c.30C>T	p.Gly10Gly	synonymous	Exon 1 of 39	ENSP00000347719.4	Q9BTW9-1
	TBCD	ENST00000684760.1		c.30C>T	p.Gly10Gly	synonymous	Exon 1 of 40	ENSP00000507696.1	A0A804HJY5
	TBCD	ENST00000684349.1		c.30C>T	p.Gly10Gly	synonymous	Exon 1 of 39	ENSP00000508067.1	A0A804HKT8

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2314 AN: 152134 Hom.: 30 Cov.: 33

Gnomad AFR AF: 0.00362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0164 AC: 1887 AN: 115256 AF XY: 0.0162

Gnomad AFR exome AF: 0.00113

Gnomad AMR exome AF: 0.00517

Gnomad ASJ exome AF: 0.0179

Gnomad EAS exome AF: 0.0310

Gnomad FIN exome AF: 0.0352

Gnomad NFE exome AF: 0.0212

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.0207 AC: 28434 AN: 1371978 Hom.: 347 Cov.: 31 AF XY: 0.0203 AC XY: 13722 AN XY: 676988

African (AFR) AF: 0.00266 AC: 75 AN: 28222

American (AMR) AF: 0.00576 AC: 195 AN: 33846

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 407 AN: 24356

East Asian (EAS) AF: 0.0450 AC: 1456 AN: 32362

South Asian (SAS) AF: 0.00644 AC: 499 AN: 77498

European-Finnish (FIN) AF: 0.0336 AC: 1462 AN: 43480

Middle Eastern (MID) AF: 0.00136 AC: 6 AN: 4396

European-Non Finnish (NFE) AF: 0.0218 AC: 23357 AN: 1070870

Other (OTH) AF: 0.0172 AC: 977 AN: 56948

GnomAD4 genome AF: 0.0152 AC: 2311 AN: 152248 Hom.: 30 Cov.: 33 AF XY: 0.0156 AC XY: 1158 AN XY: 74432

African (AFR) AF: 0.00361 AC: 150 AN: 41570

American (AMR) AF: 0.00928 AC: 142 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5176

South Asian (SAS) AF: 0.00579 AC: 28 AN: 4832

European-Finnish (FIN) AF: 0.0333 AC: 353 AN: 10598

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0208 AC: 1413 AN: 67978

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.0173 Hom.: 10

Bravo AF: 0.0130

Asia WGS AF: 0.0120 AC: 40 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.87
PhyloP100		0.20
PromoterAI		-0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs11550067; hg19: chr17-80710099; COSMIC: COSV56182363; COSMIC: COSV56182363;