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. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281.3. 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
	TBCB	NM_001281.3	MANE Select	c.26C>A	p.Pro9His	missense	Exon 1 of 6	NP_001272.2	Q99426-1
	TBCB	NR_155756.2		n.620C>A		non_coding_transcript_exon	Exon 1 of 6
	TBCB	NM_001300971.3		c.-382C>A		upstream_gene	N/A	NP_001287900.1	Q99426-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCB	ENST00000221855.8	TSL:1 MANE Select	c.26C>A	p.Pro9His	missense	Exon 1 of 6	ENSP00000221855.3	Q99426-1
	TBCB	ENST00000651435.1		c.26C>A	p.Pro9His	missense	Exon 1 of 7	ENSP00000498740.1	A0A494C0X0
	TBCB	ENST00000888742.1		c.26C>A	p.Pro9His	missense	Exon 1 of 7	ENSP00000558801.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 241926 AF XY: 0.00000760

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 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

African (AFR) AF: 0.0000600 AC: 2 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 85416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110374

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.61
Sift	Benign	0.043	D
Sift4G	Benign	0.063	T
Polyphen		1.0	D
Vest4		0.47
MutPred		0.44		Loss of loop (P = 0.0203)
MVP		0.97
MPC		1.4
ClinPred		0.99	D
GERP RS		5.4
PromoterAI		0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.44
gMVP		0.32
Mutation Taster		=66/34	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: rs778882737; hg19: chr19-36606488;