rs778882737

Variant names:

• chr19-36115586-C-A
• rs778882737
• NM_001281.3:c.26C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-36115586-C-A
• chr19-36115586-C-T

Variant summary

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

The NM_001281.3(TBCB):​c.26C>A​(p.Pro9His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,586 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P9L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TBCB NM_001281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55

Genes affected

TBCB (HGNC:1989): (tubulin folding cofactor B) Predicted to be involved in cell differentiation and nervous system development. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCB	NM_001281.3	c.26C>A	p.Pro9His	missense_variant	Exon 1 of 6	ENST00000221855.8	NP_001272.2
TBCB	NR_155756.2	n.620C>A		non_coding_transcript_exon_variant	Exon 1 of 6
TBCB	NM_001300971.3	c.-382C>A		upstream_gene_variant			NP_001287900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCB	ENST00000221855.8	c.26C>A	p.Pro9His	missense_variant	Exon 1 of 6	1	NM_001281.3	ENSP00000221855.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000413 AC: 1 AN: 241926 Hom.: 0 AF XY: 0.00000760 AC XY: 1 AN XY: 131540

Gnomad AFR exome AF: 0.0000673

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457586 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724714

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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	0.33
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T;T
M_CAP	Pathogenic	0.51	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Uncertain	0.61
Sift	Benign	0.043	D;.
Sift4G	Benign	0.063	T;D
Polyphen		1.0	D;.
Vest4		0.47
MutPred		0.44		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.97
MPC		1.4
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.44
gMVP		0.32

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: rs778882737; hg19: chr19-36606488;