16-29841539-C-A

Variant names:

• chr16-29841539-C-A
• rs3815824
• NM_005115.5:c.1192-57C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005115.5(MVP):​c.1192-57C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000293 in 1,366,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: MVP NM_005115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVP	NM_005115.5	c.1192-57C>A		intron_variant	Intron 8 of 14	ENST00000357402.10	NP_005106.2
MVP	NM_017458.3	c.1192-57C>A		intron_variant	Intron 8 of 14		NP_059447.2
MVP	NM_001293204.1	c.1192-57C>A		intron_variant	Intron 7 of 13		NP_001280133.1
MVP	NM_001293205.1	c.1192-57C>A		intron_variant	Intron 7 of 12		NP_001280134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10	c.1192-57C>A		intron_variant	Intron 8 of 14	1	NM_005115.5	ENSP00000349977.5
MVP	ENST00000395353.5	c.1192-57C>A		intron_variant	Intron 8 of 14	5		ENSP00000378760.1
MVP	ENST00000563558.5	c.379-57C>A		intron_variant	Intron 4 of 4	4		ENSP00000454825.1
MVP	ENST00000568068.1	n.367-57C>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000293 AC: 4 AN: 1366504 Hom.: 0 AF XY: 0.00000149 AC XY: 1 AN XY: 669270

African (AFR) AF: 0.00 AC: 0 AN: 30490

American (AMR) AF: 0.0000638 AC: 2 AN: 31370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20240

East Asian (EAS) AF: 0.00 AC: 0 AN: 38830

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 71004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3736

European-Non Finnish (NFE) AF: 9.38e-7 AC: 1 AN: 1066072

Other (OTH) AF: 0.00 AC: 0 AN: 56120

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.60
PhyloP100		-0.77

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

Other links and lift over

dbSNP: rs3815824; hg19: chr16-29852860;