chr17-82752209-G-C

Variant names:

• chr17-82752209-G-C
• rs1010575243
• NM_005993.5:c.16G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005993.5(TBCD):​c.16G>C​(p.Glu6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBCD NM_005993.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15136874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCD	NM_005993.5	c.16G>C	p.Glu6Gln	missense_variant	Exon 1 of 39	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9	c.16G>C	p.Glu6Gln	missense_variant	Exon 1 of 39	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.36	T;T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.46	N;.
REVEL	Benign	0.053
Sift	Benign	0.42	T;.
Sift4G	Benign	0.41	T;T
Polyphen		0.25	B;.
Vest4		0.074
MutPred		0.077		Loss of glycosylation at S4 (P = 0.1753);Loss of glycosylation at S4 (P = 0.1753);
MVP		0.36
MPC		0.63
ClinPred		0.10	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.33

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: rs1010575243; hg19: chr17-80710085;