Variant 17-18804169-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016078.6(TVP23B):c.494G>T(p.Gly165Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TVP23B
NM_016078.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.60

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:

TVP23B (HGNC:):

TVP23B links:

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ACMG classification

Classification made for transcript

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
TVP23B	NM_016078.6 linkuse as main transcript	c.494G>T	p.Gly165Val	missense_variant	6/7	ENST00000307767.13	NP_057162.4	Q9NYZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TVP23B	ENST00000307767.13 linkuse as main transcript	c.494G>T	p.Gly165Val	missense_variant	6/7	1	NM_016078.6	ENSP00000305654.8		Q9NYZ1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248966

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135072

show subpopulations

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Feb 07, 2023

The c.494G>T (p.G165V) alteration is located in exon 6 (coding exon 6) of the TVP23B gene. This alteration results from a G to T substitution at nucleotide position 494, causing the glycine (G) at amino acid position 165 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

T;T;T;T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;D;.;D

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.62

D;D;D;D;D

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.1

M;.;.;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.6

D;.;.;.;.

REVEL

Uncertain

0.32

Sift

Benign

0.065

T;.;.;.;.

Sift4G

Benign

0.18

T;T;T;T;T

Polyphen

0.99

D;.;.;.;.

Vest4

0.71

MutPred

0.65

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;.;.;

MVP

0.31

MPC

1.0

ClinPred

0.82

GERP RS

2.7

Varity_R

0.46

gMVP

0.65

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