19-36121691-C-T

Variant names:

• chr19-36121691-C-T
• rs1425374917
• NM_001281.3:c.520C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001281.3(TBCB):​c.520C>T​(p.Pro174Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,402,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. P174A) 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: 0.643

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056898057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCB	NM_001281.3	c.520C>T	p.Pro174Ser	missense_variant	Exon 4 of 6	ENST00000221855.8	NP_001272.2
TBCB	NM_001300971.3	c.367C>T	p.Pro123Ser	missense_variant	Exon 4 of 6		NP_001287900.1
TBCB	NR_155756.2	n.1114C>T		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCB	ENST00000221855.8	c.520C>T	p.Pro174Ser	missense_variant	Exon 4 of 6	1	NM_001281.3	ENSP00000221855.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000640 AC: 1 AN: 156148 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 84810

Gnomad AFR exome AF: 0.00

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: 0.0000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1402786 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 692642

Gnomad4 AFR exome AF: 0.00

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.50
DEOGEN2	Benign	0.29	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	-0.060	N;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.12
Sift	Benign	0.74	T;.;.
Sift4G	Benign	0.72	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.039
MutPred		0.24		Gain of phosphorylation at P174 (P = 0.0587);.;.;
MVP		0.63
MPC		0.55
ClinPred		0.041	T
GERP RS		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.024
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1425374917; hg19: chr19-36612593;