chr16-29830589-C-T

Position:

chr16-29830589-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005115.5(MVP):c.40C>T(p.His14Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MVP
NM_005115.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

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:

ENSG00000281348 (HGNC:):

ENSG00000281348 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.122026294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVP	NM_005115.5 linkuse as main transcript	c.40C>T	p.His14Tyr	missense_variant	2/15	ENST00000357402.10	NP_005106.2	Q14764X5D2M8
MVP	NM_017458.3 linkuse as main transcript	c.40C>T	p.His14Tyr	missense_variant	2/15		NP_059447.2	Q14764X5D2M8
MVP	NM_001293204.1 linkuse as main transcript	c.40C>T	p.His14Tyr	missense_variant	1/14		NP_001280133.1	Q14764X5DNU0
MVP	NM_001293205.1 linkuse as main transcript	c.40C>T	p.His14Tyr	missense_variant	1/13		NP_001280134.1	Q14764X5D7K9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MVP	ENST00000357402.10 linkuse as main transcript	c.40C>T	p.His14Tyr	missense_variant	2/15	1	NM_005115.5	ENSP00000349977.5	Q14764
ENSG00000281348	ENST00000562285.1 linkuse as main transcript	n.*264C>T		non_coding_transcript_exon_variant	3/3	2		ENSP00000457363.1	H3BTX0
ENSG00000281348	ENST00000562285.1 linkuse as main transcript	n.*264C>T		3_prime_UTR_variant	3/3	2		ENSP00000457363.1	H3BTX0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000771

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

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251378

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

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

Mar 30, 2024

The c.40C>T (p.H14Y) alteration is located in exon 2 (coding exon 1) of the MVP gene. This alteration results from a C to T substitution at nucleotide position 40, causing the histidine (H) at amino acid position 14 to be replaced by a tyrosine (Y). 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

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.035

T;T;T;T;.;.;.;T;.

Eigen

Benign

-0.093

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;.;D;D;D;D;D;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.12

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.66

.;N;N;.;.;.;.;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N;N;.

REVEL

Benign

0.16

Sift

Benign

0.32

T;T;T;T;T;T;T;T;.

Sift4G

Benign

0.43

T;T;T;T;T;T;T;T;T

Polyphen

0.074

.;B;B;.;.;.;.;.;.

Vest4

0.32, 0.32, 0.35

MVP

0.37

MPC

0.41

ClinPred

0.11

GERP RS

5.8

Varity_R

0.15

gMVP

0.62

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