chr16-29833824-T-A

Position:

• chr16-29833824-T-A

Variant summary

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

The NM_005115.5(MVP):​c.413T>A​(p.Val138Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,884 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: 0.0000021 (0 hom.)
• Consequence: MVP NM_005115.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.47

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 (HGNC:):

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	Protein	UniProt
MVP	NM_005115.5	c.413T>A	p.Val138Glu	missense_variant	4/15	ENST00000357402.10	NP_005106.2
MVP	NM_017458.3	c.413T>A	p.Val138Glu	missense_variant	4/15		NP_059447.2
MVP	NM_001293204.1	c.413T>A	p.Val138Glu	missense_variant	3/14		NP_001280133.1
MVP	NM_001293205.1	c.413T>A	p.Val138Glu	missense_variant	3/13		NP_001280134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10	c.413T>A	p.Val138Glu	missense_variant	4/15	1	NM_005115.5	ENSP00000349977.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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

Dec 19, 2022

The c.413T>A (p.V138E) alteration is located in exon 4 (coding exon 3) of the MVP gene. This alteration results from a T to A substitution at nucleotide position 413, causing the valine (V) at amino acid position 138 to be replaced by a glutamic acid (E). 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	0.34
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;D;D;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;.;D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.8	.;M;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.050	D;T;T;T
Sift4G	Uncertain	0.0060	D;T;T;D
Polyphen		0.98	.;D;D;.
Vest4		0.70, 0.71
MutPred		0.56		Gain of disorder (P = 0.0018);Gain of disorder (P = 0.0018);Gain of disorder (P = 0.0018);Gain of disorder (P = 0.0018);
MVP		0.65
MPC		0.99
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.37
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29845145;