chr16-29830906-A-T

Position:

• chr16-29830906-A-T

Variant summary

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

The NM_005115.5(MVP):​c.154A>T​(p.Thr52Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,008 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96

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.154A>T	p.Thr52Ser	missense_variant	3/15	ENST00000357402.10	NP_005106.2
MVP	NM_017458.3	c.154A>T	p.Thr52Ser	missense_variant	3/15		NP_059447.2
MVP	NM_001293204.1	c.154A>T	p.Thr52Ser	missense_variant	2/14		NP_001280133.1
MVP	NM_001293205.1	c.154A>T	p.Thr52Ser	missense_variant	2/13		NP_001280134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10	c.154A>T	p.Thr52Ser	missense_variant	3/15	1	NM_005115.5	ENSP00000349977.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461008 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726626

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Sep 03, 2024

The c.154A>T (p.T52S) alteration is located in exon 3 (coding exon 2) of the MVP gene. This alteration results from a A to T substitution at nucleotide position 154, causing the threonine (T) at amino acid position 52 to be replaced by a serine (S). 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	0.20
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;T;T;T;.;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;.;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;L;.;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.31	T;T;T;T;T;T;T
Sift4G	Benign	0.077	T;T;T;T;T;T;T
Polyphen		0.93	.;P;P;.;.;.;.
Vest4		0.40, 0.40
MutPred		0.58		Loss of glycosylation at T52 (P = 0.0587);Loss of glycosylation at T52 (P = 0.0587);Loss of glycosylation at T52 (P = 0.0587);Loss of glycosylation at T52 (P = 0.0587);Loss of glycosylation at T52 (P = 0.0587);Loss of glycosylation at T52 (P = 0.0587);Loss of glycosylation at T52 (P = 0.0587);
MVP		0.34
MPC		0.40
ClinPred		0.78	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.30

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

Other links and lift over

dbSNP: rs2067436527; hg19: chr16-29842227;