Variant chr16-29834013-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_005115.5(MVP):c.524G>T(p.Arg175Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MVP
NM_005115.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

MVP (HGNC:7531): (major vault protein) This gene encodes the major component of the vault complex. Vaults are multi-subunit ribonucleoprotein structures that may be involved in nucleo-cytoplasmic transport. The encoded protein may play a role in multiple cellular processes by regulating the MAP kinase, JAK/STAT and phosphoinositide 3-kinase/Akt signaling pathways. The encoded protein also plays a role in multidrug resistance, and expression of this gene may be a prognostic marker for several types of cancer. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

MVP links:

MVP (HGNC:):

MVP 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
MVP	NM_005115.5 linkuse as main transcript	c.524G>T	p.Arg175Leu	missense_variant	5/15	ENST00000357402.10	NP_005106.2	Q14764X5D2M8
MVP	NM_017458.3 linkuse as main transcript	c.524G>T	p.Arg175Leu	missense_variant	5/15		NP_059447.2	Q14764X5D2M8
MVP	NM_001293204.1 linkuse as main transcript	c.524G>T	p.Arg175Leu	missense_variant	4/14		NP_001280133.1	Q14764X5DNU0
MVP	NM_001293205.1 linkuse as main transcript	c.524G>T	p.Arg175Leu	missense_variant	4/13		NP_001280134.1	Q14764X5D7K9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10 linkuse as main transcript	c.524G>T	p.Arg175Leu	missense_variant	5/15	1	NM_005115.5	ENSP00000349977.5		Q14764

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251250

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000288

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000279

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jan 03, 2024

The c.524G>T (p.R175L) alteration is located in exon 5 (coding exon 4) of the MVP gene. This alteration results from a G to T substitution at nucleotide position 524, causing the arginine (R) at amino acid position 175 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

Benign

0.23

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;D;D

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;.

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

.;M;M

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Uncertain

0.37

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

1.0

.;D;D

Vest4

0.78, 0.79

MutPred

0.55

Loss of MoRF binding (P = 0.0367);Loss of MoRF binding (P = 0.0367);Loss of MoRF binding (P = 0.0367);

MVP

0.66

MPC

1.3

ClinPred

0.88

GERP RS

6.0

Varity_R

0.29

gMVP

0.76

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