17-82752235-G-A

Variant names:

• chr17-82752235-G-A
• rs1568079966
• NM_005993.5:c.42G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005993.5(TBCD):​c.42G>A​(p.Glu14Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,373,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TBCD NM_005993.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.177
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-82752235-G-A is Benign according to our data. Variant chr17-82752235-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2779055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.177 with no splicing effect.

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.42G>A	p.Glu14Glu	synonymous	Exon 1 of 39	NP_005984.3
	TBCD	NM_001411101.1		c.42G>A	p.Glu14Glu	synonymous	Exon 1 of 38	NP_001398030.1	A0A804HLI2
	TBCD	NM_001411102.1		c.42G>A	p.Glu14Glu	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.42G>A	p.Glu14Glu	synonymous	Exon 1 of 39	ENSP00000347719.4	Q9BTW9-1
	TBCD	ENST00000684760.1		c.42G>A	p.Glu14Glu	synonymous	Exon 1 of 40	ENSP00000507696.1	A0A804HJY5
	TBCD	ENST00000684349.1		c.42G>A	p.Glu14Glu	synonymous	Exon 1 of 39	ENSP00000508067.1	A0A804HKT8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000102 AC: 14 AN: 1373982 Hom.: 0 Cov.: 31 AF XY: 0.00000737 AC XY: 5 AN XY: 678018

African (AFR) AF: 0.00 AC: 0 AN: 28460

American (AMR) AF: 0.00 AC: 0 AN: 34310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24488

East Asian (EAS) AF: 0.00 AC: 0 AN: 32752

South Asian (SAS) AF: 0.00 AC: 0 AN: 77770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4340

European-Non Finnish (NFE) AF: 0.0000112 AC: 12 AN: 1072220

Other (OTH) AF: 0.0000351 AC: 2 AN: 57044

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000380 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.7
DANN	Benign	0.93
PhyloP100		-0.18
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs1568079966; hg19: chr17-80710111;