19-44647519-GTC-ATA

Variant names:

• chr19-44647519-GTC-ATA
• NM_006505.5:c.376_378delGTCinsATA
• PVR p.Val126Ile

Variant summary

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

The NM_006505.5(PVR):​c.376_378delGTCinsATA​(p.Val126Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PVR NM_006505.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 0 publications found

Genes affected

PVR (HGNC:9705): (PVR cell adhesion molecule) The protein encoded by this gene is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006505.5. 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
	PVR	NM_006505.5	MANE Select	c.376_378delGTCinsATA	p.Val126Ile	missense	N/A	NP_006496.4
	PVR	NM_001135770.4		c.376_378delGTCinsATA	p.Val126Ile	missense	N/A	NP_001129242.2	A0A0A0MSA9
	PVR	NM_001135768.3		c.376_378delGTCinsATA	p.Val126Ile	missense	N/A	NP_001129240.1	P15151-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVR	ENST00000425690.8	TSL:1 MANE Select	c.376_378delGTCinsATA	p.Val126Ile	missense	N/A	ENSP00000402060.2	A0A0C4DG49
	PVR	ENST00000406449.8	TSL:1	c.376_378delGTCinsATA	p.Val126Ile	missense	N/A	ENSP00000383907.3	A0A0A0MSA9
	PVR	ENST00000971445.1		c.376_378delGTCinsATA	p.Val126Ile	missense	N/A	ENSP00000641504.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

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: chr19-45150791;