Variant 17-18789405-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001316919.1(TVP23B):c.-128C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

TVP23B
NM_001316919.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.258

Variant links:

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]

TVP23B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.023415118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TVP23B	NM_016078.6 link	c.65C>T	p.Thr22Met	missense_variant	2/7	ENST00000307767.13	NP_057162.4	Q9NYZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TVP23B	ENST00000307767.13 link	c.65C>T	p.Thr22Met	missense_variant	2/7	1	NM_016078.6	ENSP00000305654.8		Q9NYZ1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000171

AC:

AN:

251166

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000249

AC:

364

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

187

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000296

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000309

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000300

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

The c.65C>T (p.T22M) alteration is located in exon 2 (coding exon 2) of the TVP23B gene. This alteration results from a C to T substitution at nucleotide position 65, causing the threonine (T) at amino acid position 22 to be replaced by a methionine (M). 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

0.079

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.012

Sift

Benign

0.12

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.31

B;.

Vest4

0.12

MVP

0.030

MPC

0.046

ClinPred

0.024

GERP RS

2.8

Varity_R

0.033

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over