16-29830629-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005115.5(MVP):c.80G>A(p.Arg27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,614,034 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (14 hom., cov: 31)
  • Exomes 𝑓: 0.00075 (20 hom.)
• Consequence: MVP NM_005115.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006412536).
• BP6: Variant 16-29830629-G-A is Benign according to our data. Variant chr16-29830629-G-A is described in ClinVar as [Benign]. Clinvar id is 778608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00718 (1092/152182) while in subpopulation AFR AF= 0.0251 (1041/41514). AF 95% confidence interval is 0.0238. There are 14 homozygotes in gnomad4. There are 531 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MVP	NM_005115.5	c.80G>A	p.Arg27His	missense_variant	2/15	ENST00000357402.10
MVP	NM_017458.3	c.80G>A	p.Arg27His	missense_variant	2/15
MVP	NM_001293204.1	c.80G>A	p.Arg27His	missense_variant	1/14
MVP	NM_001293205.1	c.80G>A	p.Arg27His	missense_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MVP	ENST00000357402.10	c.80G>A	p.Arg27His	missense_variant	2/15	1	NM_005115.5	P1

Frequencies

GnomAD3 genomes AF: 0.00720 AC: 1095 AN: 152064 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00206 AC: 517 AN: 251304 Hom.: 7 AF XY: 0.00136 AC XY: 185 AN XY: 135822

Gnomad AFR exome AF: 0.0283

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000753 AC: 1101 AN: 1461852 Hom.: 20 Cov.: 31 AF XY: 0.000619 AC XY: 450 AN XY: 727240

Gnomad4 AFR exome AF: 0.0272

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000423

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.00718 AC: 1092 AN: 152182 Hom.: 14 Cov.: 31 AF XY: 0.00714 AC XY: 531 AN XY: 74398

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00132 Hom.: 6

Bravo AF: 0.00869

ESP6500AA AF: 0.0255 AC: 112

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00268 AC: 325

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.17	T;D;D;T;.;.;.;T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.82	T;T;.;T;T;T;T;T;T
MetaRNN	Benign	0.0064	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	0.98	D;D;N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D;D;D;.
Sift	Benign	0.038	D;T;T;D;D;T;D;D;.
Sift4G	Uncertain	0.018	D;T;T;D;D;D;T;D;D
Polyphen		0.21	.;B;B;.;.;.;.;.;.
Vest4		0.28, 0.29, 0.22
MVP		0.41
MPC		0.44
ClinPred		0.057	T
GERP RS		0.47
Varity_R		0.088
gMVP		0.51

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: rs142997389; hg19: chr16-29841950;