rs181969865

Variant names:

• chr17-82924992-C-A
• NM_005993.5:c.2314C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-82924992-C-A
• chr17-82924992-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005993.5(TBCD):​c.2314C>A​(p.Arg772Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,423,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TBCD NM_005993.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.39

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCD	NM_005993.5	c.2314C>A	p.Arg772Ser	missense_variant	Exon 27 of 39	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9	c.2314C>A	p.Arg772Ser	missense_variant	Exon 27 of 39	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1423434 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 704408

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;.;.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.1	M;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.0	D;.;.;.;.
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0030	D;.;.;.;.
Sift4G	Benign	0.11	T;T;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.96
MutPred		0.63		Gain of glycosylation at R772 (P = 0.0288);Gain of glycosylation at R772 (P = 0.0288);.;.;.;
MVP		0.82
MPC		1.1
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80882868;