PLVAP p.Arg358Arg

Variant names:

• chr19-17365390-C-C
• NM_031310.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-17365391--
• chr19-17365391-T-A
• chr19-17365391-T-G
• chr19-17365391-T-C
• chr19-17365393-G-T
• chr19-17365391-TCG-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031310.3(PLVAP):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLVAP NM_031310.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.79
• Publications: 0 publications found

Genes affected

PLVAP (HGNC:13635): (plasmalemma vesicle associated protein) Predicted to enable identical protein binding activity. Involved in MAPK cascade; positive regulation of cellular extravasation; and tumor necrosis factor-mediated signaling pathway. Located in cell surface. Colocalizes with caveola. Implicated in congenital diarrhea. [provided by Alliance of Genome Resources, Apr 2022]

PLVAP Gene-Disease associations (from GenCC):

• diarrhea 10, protein-losing enteropathy type

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital diarrhea 7 with exudative enteropathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031310.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLVAP	NM_031310.3	MANE Select	c.		exon_region	Exon 3 of 6	NP_112600.1	Q9BX97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLVAP	ENST00000252590.9	TSL:1 MANE Select	c.		exon_region	Exon 3 of 6	ENSP00000252590.3	Q9BX97
	PLVAP	ENST00000962152.1		c.		exon_region	Exon 3 of 7	ENSP00000632211.1
	PLVAP	ENST00000962153.1		c.		exon_region	Exon 3 of 6	ENSP00000632212.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-17476199;