19-36120777-T-C

Position:

• chr19-36120777-T-C

Variant summary

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

The NM_001281.3(TBCB):​c.326T>C​(p.Ile109Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TBCB NM_001281.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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/exons	MANE	Protein	UniProt
TBCB	NM_001281.3	c.326T>C	p.Ile109Thr	missense_variant	3/6	ENST00000221855.8	NP_001272.2
TBCB	NM_001300971.3	c.173T>C	p.Ile58Thr	missense_variant	3/6		NP_001287900.1
TBCB	NR_155756.2	n.920T>C		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCB	ENST00000221855.8	c.326T>C	p.Ile109Thr	missense_variant	3/6	1	NM_001281.3	ENSP00000221855	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.326T>C (p.I109T) alteration is located in exon 3 (coding exon 3) of the TBCB gene. This alteration results from a T to C substitution at nucleotide position 326, causing the isoleucine (I) at amino acid position 109 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T;T;T;.
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Uncertain	2.9	M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D;.;.;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0040	D;.;.;.
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.19	B;.;.;.
Vest4		0.20
MutPred		0.61		Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);.;.;
MVP		0.91
MPC		0.81
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.17
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-36611679;