19-36121539-C-A

Variant names:

• chr19-36121539-C-A
• rs778026150
• NM_001281.3:c.368C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001281.3(TBCB):​c.368C>A​(p.Ser123Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000711 in 1,406,604 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. S123C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TBCB NM_001281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.44
• 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.368C>A	p.Ser123Tyr	missense	Exon 4 of 6	NP_001272.2	Q99426-1
	TBCB	NM_001300971.3		c.215C>A	p.Ser72Tyr	missense	Exon 4 of 6	NP_001287900.1	Q99426-2
	TBCB	NR_155756.2		n.962C>A		non_coding_transcript_exon	Exon 4 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCB	ENST00000221855.8	TSL:1 MANE Select	c.368C>A	p.Ser123Tyr	missense	Exon 4 of 6	ENSP00000221855.3	Q99426-1
	TBCB	ENST00000588385.5	TSL:1	c.215C>A	p.Ser72Tyr	missense	Exon 3 of 5	ENSP00000467172.1	K7EP07
	TBCB	ENST00000651435.1		c.368C>A	p.Ser123Tyr	missense	Exon 4 of 7	ENSP00000498740.1	A0A494C0X0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406604 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 695314

African (AFR) AF: 0.00 AC: 0 AN: 32126

American (AMR) AF: 0.00 AC: 0 AN: 37426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25234

East Asian (EAS) AF: 0.00 AC: 0 AN: 36702

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085744

Other (OTH) AF: 0.00 AC: 0 AN: 58342

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.30	T
Polyphen		0.69	P
Vest4		0.56
MutPred		0.34		Loss of phosphorylation at S123 (P = 0.0505)
MVP		0.95
MPC		0.98
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.66
Mutation Taster		=56/44	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: rs778026150; hg19: chr19-36612441;