16-29836797-C-G

Variant summary

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

The NM_005115.5(MVP):c.748C>G(p.Leu250Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MVP NM_005115.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08

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]

ACMG classification

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	UniProt
MVP	NM_005115.5	c.748C>G	p.Leu250Val	missense_variant	7/15	ENST00000357402.10
MVP	NM_017458.3	c.748C>G	p.Leu250Val	missense_variant	7/15
MVP	NM_001293204.1	c.748C>G	p.Leu250Val	missense_variant	6/14
MVP	NM_001293205.1	c.748C>G	p.Leu250Val	missense_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MVP	ENST00000357402.10	c.748C>G	p.Leu250Val	missense_variant	7/15	1	NM_005115.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.748C>G (p.L250V) alteration is located in exon 7 (coding exon 6) of the MVP gene. This alteration results from a C to G substitution at nucleotide position 748, causing the leucine (L) at amino acid position 250 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	0.30
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Uncertain	26
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D;D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.97	D;.
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.8	M;M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.57
MutPred		0.66		Gain of MoRF binding (P = 0.1038);Gain of MoRF binding (P = 0.1038);
MVP		0.61
MPC		0.47
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.47
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29848118;