chr16-29830949-C-G

Position:

• chr16-29830949-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005115.5(MVP):​c.197C>G​(p.Ser66Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MVP NM_005115.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00700

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09236881).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVP	NM_005115.5	c.197C>G	p.Ser66Cys	missense_variant	3/15	ENST00000357402.10	NP_005106.2
MVP	NM_017458.3	c.197C>G	p.Ser66Cys	missense_variant	3/15		NP_059447.2
MVP	NM_001293204.1	c.197C>G	p.Ser66Cys	missense_variant	2/14		NP_001280133.1
MVP	NM_001293205.1	c.197C>G	p.Ser66Cys	missense_variant	2/13		NP_001280134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10	c.197C>G	p.Ser66Cys	missense_variant	3/15	1	NM_005115.5	ENSP00000349977.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Nov 12, 2024

The c.197C>G (p.S66C) alteration is located in exon 3 (coding exon 2) of the MVP gene. This alteration results from a C to G substitution at nucleotide position 197, causing the serine (S) at amino acid position 66 to be replaced by a cysteine (C). 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	0.063
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.0089	T;T;T;T;.;.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.78	T;T;.;T;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.092	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;N;.;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.12	N;N;N;N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.055	T;D;D;T;D;T;T
Sift4G	Uncertain	0.047	D;T;T;T;T;T;T
Polyphen		0.0	.;B;B;.;.;.;.
Vest4		0.27
MutPred		0.37		Loss of glycosylation at S66 (P = 0.082);Loss of glycosylation at S66 (P = 0.082);Loss of glycosylation at S66 (P = 0.082);Loss of glycosylation at S66 (P = 0.082);Loss of glycosylation at S66 (P = 0.082);Loss of glycosylation at S66 (P = 0.082);Loss of glycosylation at S66 (P = 0.082);
MVP		0.26
MPC		0.34
ClinPred		0.065	T
GERP RS		1.0
Varity_R		0.044
gMVP		0.39

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: chr16-29842270;