19-44658770-G-T

Variant names:

• chr19-44658770-G-T
• rs203710
• NM_006505.5:c.1020G>T

Variant summary

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

The NM_006505.5(PVR):​c.1020G>T​(p.Met340Ile) 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. 6/7 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: 32)
• Consequence: PVR NM_006505.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 28 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: 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 (MetaRNN=0.045244843).

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.1020G>T	p.Met340Ile	missense	Exon 6 of 8	NP_006496.4
	PVR	NM_001135770.4		c.1020G>T	p.Met340Ile	missense	Exon 6 of 6	NP_001129242.2	A0A0A0MSA9
	PVR	NM_001135768.3		c.1015+5G>T		splice_region intron	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.1020G>T	p.Met340Ile	missense	Exon 6 of 8	ENSP00000402060.2	A0A0C4DG49
	PVR	ENST00000406449.8	TSL:1	c.1020G>T	p.Met340Ile	missense	Exon 6 of 6	ENSP00000383907.3	A0A0A0MSA9
	PVR	ENST00000971445.1		c.1101G>T	p.Met367Ile	missense	Exon 6 of 8	ENSP00000641504.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.022
DEOGEN2	Benign	0.0077	T
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.045	T
PhyloP100		-2.0
Sift4G	Benign	0.48	T
Vest4		0.048
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs203710; hg19: chr19-45162038;