19-36116167-G-A

Position:

• chr19-36116167-G-A

Variant summary

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

The NM_001281.3(TBCB):​c.241G>A​(p.Asp81Asn) variant causes a missense change. 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: 6.46

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.241G>A	p.Asp81Asn	missense_variant	2/6	ENST00000221855.8	NP_001272.2
TBCB	NM_001300971.3	c.88G>A	p.Asp30Asn	missense_variant	2/6		NP_001287900.1
TBCB	NR_155756.2	n.835G>A		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCB	ENST00000221855.8	c.241G>A	p.Asp81Asn	missense_variant	2/6	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

Apr 26, 2024

The c.241G>A (p.D81N) alteration is located in exon 2 (coding exon 2) of the TBCB gene. This alteration results from a G to A substitution at nucleotide position 241, causing the aspartic acid (D) at amino acid position 81 to be replaced by an asparagine (N). 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	Benign	0.10
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;T;T;T;.;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D;T;D;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Benign	1.8	L;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.4	D;.;.;.;.;.;.
REVEL	Uncertain	0.50
Sift	Benign	0.074	T;.;.;.;.;.;.
Sift4G	Benign	0.080	T;T;T;T;T;T;T
Polyphen		0.80	P;.;.;.;.;.;.
Vest4		0.38
MutPred		0.54		Loss of catalytic residue at D81 (P = 0.1714);.;Loss of catalytic residue at D81 (P = 0.1714);.;.;.;.;
MVP		0.91
MPC		0.62
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.46
gMVP		0.44

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: chr19-36607069;