Genetic Variant MVP:p.Arg766Leu (chr16-29847228-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005115.5(MVP):c.2297G>T(p.Arg766Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MVP
NM_005115.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.19

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MVP	NM_005115.5 link	c.2297G>T	p.Arg766Leu	missense_variant	Exon 14 of 15	ENST00000357402.10	NP_005106.2
MVP	NM_017458.3 link	c.2297G>T	p.Arg766Leu	missense_variant	Exon 14 of 15		NP_059447.2
MVP	NM_001293205.1 link	c.2099G>T	p.Arg700Leu	missense_variant	Exon 12 of 13		NP_001280134.1
MVP	NM_001293204.1 link	c.2235-118G>T		intron_variant	Intron 12 of 13		NP_001280133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10 link	c.2297G>T	p.Arg766Leu	missense_variant	Exon 14 of 15	1	NM_005115.5	ENSP00000349977.5
MVP	ENST00000395353.5 link	c.2297G>T	p.Arg766Leu	missense_variant	Exon 14 of 15	5		ENSP00000378760.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461498

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111988

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

D;D

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.69

T;.

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M

PhyloP100

4.2

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Benign

0.14

Sift

Uncertain

0.029

D;D

Sift4G

Uncertain

0.050

T;T

Polyphen

1.0

D;D

Vest4

0.55

MutPred

0.36

Loss of MoRF binding (P = 0.0585);Loss of MoRF binding (P = 0.0585);

MVP

0.47

MPC

1.3

ClinPred

0.98

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.35

gMVP

0.82

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over