17-18798885-C-T

Position:

• chr17-18798885-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016078.6(TVP23B):​c.404C>T​(p.Pro135Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TVP23B NM_016078.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32

Genes affected

TVP23B (HGNC:20399): (trans-golgi network vesicle protein 23 homolog B) Predicted to be involved in protein secretion and vesicle-mediated transport. Predicted to be integral component of membrane. Predicted to be integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TVP23B	NM_016078.6	c.404C>T	p.Pro135Leu	missense_variant	5/7	ENST00000307767.13	NP_057162.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TVP23B	ENST00000307767.13	c.404C>T	p.Pro135Leu	missense_variant	5/7	1	NM_016078.6	ENSP00000305654.8

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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

Aug 28, 2024

The c.404C>T (p.P135L) alteration is located in exon 5 (coding exon 5) of the TVP23B gene. This alteration results from a C to T substitution at nucleotide position 404, causing the proline (P) at amino acid position 135 to be replaced by a leucine (L). 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	Uncertain	0.38
BayesDel_addAF	Benign	0.0080	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T;T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D;D;.;D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.3	M;.;.;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-8.4	D;.;.;.;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;.;.;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.92
MutPred		0.69		Gain of catalytic residue at P135 (P = 0.1107);Gain of catalytic residue at P135 (P = 0.1107);.;.;.;
MVP		0.44
MPC		1.6
ClinPred		1.0	D
GERP RS		3.1
Varity_R		0.91
gMVP		0.85

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18702198;