Variant X-155220223-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_003372.7(VBP1):c.134C>T(p.Thr45Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000251 in 1,196,602 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

VBP1
NM_003372.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

Variant links:

Genes affected

VBP1 (HGNC:12662): (VHL binding protein 1) The protein encoded by this gene interacts with the Von Hippel-Lindau protein to form an intracellular complex. The encoded protein functions as a chaperone protein, and may play a role in the transport of the Von Hippel-Lindau protein from the perinuclear granules to the nucleus or cytoplasm. Alternative splicing and the use of alternate transcription start sites results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Jan 2015]

VBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33007962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VBP1	NM_003372.7 linkuse as main transcript	c.134C>T	p.Thr45Ile	missense_variant	2/6	ENST00000286428.7	NP_003363.1
VBP1	NM_001303543.1 linkuse as main transcript	c.242C>T	p.Thr81Ile	missense_variant	2/6		NP_001290472.1
VBP1	NM_001303544.1 linkuse as main transcript	c.119C>T	p.Thr40Ile	missense_variant	3/7		NP_001290473.1
VBP1	NM_001303545.1 linkuse as main transcript	c.23C>T	p.Thr8Ile	missense_variant	2/6		NP_001290474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VBP1	ENST00000286428.7 linkuse as main transcript	c.134C>T	p.Thr45Ile	missense_variant	2/6	1	NM_003372.7	ENSP00000286428	P1	P61758-1
VBP1	ENST00000535916.5 linkuse as main transcript	c.119C>T	p.Thr40Ile	missense_variant	3/7	2		ENSP00000438694		P61758-2
VBP1	ENST00000625964.2 linkuse as main transcript	c.119C>T	p.Thr40Ile	missense_variant	2/6	5		ENSP00000486053		P61758-2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111446

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33650

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.22e-7

AC:

AN:

1085156

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

352230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000291

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111446

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33650

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

May 16, 2024

The c.134C>T (p.T45I) alteration is located in exon 2 (coding exon 2) of the VBP1 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the threonine (T) at amino acid position 45 to be replaced by an isoleucine (I). 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;.

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

.;D;D

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.7

D;.;D

REVEL

Benign

0.11

Sift

Benign

0.065

T;.;D

Sift4G

Uncertain

0.058

T;T;T

Vest4

0.35

MutPred

0.27

.;.;Gain of catalytic residue at T45 (P = 0.0178);

MVP

0.61

MPC

0.89

ClinPred

0.98

GERP RS

4.7

gMVP

0.71

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