NM_006505.5:c.1020G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006505.5(PVR):​c.1020G>A​(p.Met340Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,611,156 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 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: 𝑓 0.014 (26 hom., cov: 32)
  • Exomes 𝑓: 0.022 (409 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003705889).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0138 (2102/152314) while in subpopulation NFE AF = 0.0244 (1659/68038). AF 95% confidence interval is 0.0234. There are 26 homozygotes in GnomAd4. There are 930 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVR	NM_006505.5	MANE Select	c.1020G>A	p.Met340Ile	missense	Exon 6 of 8	NP_006496.4
	PVR	NM_001135770.4		c.1020G>A	p.Met340Ile	missense	Exon 6 of 6	NP_001129242.2
	PVR	NM_001135768.3		c.1015+5G>A		splice_region intron	N/A	NP_001129240.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVR	ENST00000425690.8	TSL:1 MANE Select	c.1020G>A	p.Met340Ile	missense	Exon 6 of 8	ENSP00000402060.2
	PVR	ENST00000406449.8	TSL:1	c.1020G>A	p.Met340Ile	missense	Exon 6 of 6	ENSP00000383907.3
	PVR	ENST00000706603.1		c.1020G>A	p.Met340Ile	missense	Exon 6 of 9	ENSP00000516465.1

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2102 AN: 152196 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.00909

GnomAD4 exome AF: 0.0217 AC: 31693 AN: 1458842 Hom.: 409 Cov.: 30 AF XY: 0.0213 AC XY: 15453 AN XY: 725976

African (AFR) AF: 0.00311 AC: 104 AN: 33416

American (AMR) AF: 0.00568 AC: 254 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000613 AC: 16 AN: 26106

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39686

South Asian (SAS) AF: 0.00700 AC: 603 AN: 86180

European-Finnish (FIN) AF: 0.00524 AC: 280 AN: 53414

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.0264 AC: 29281 AN: 1109268

Other (OTH) AF: 0.0187 AC: 1127 AN: 60290

GnomAD4 genome AF: 0.0138 AC: 2102 AN: 152314 Hom.: 26 Cov.: 32 AF XY: 0.0125 AC XY: 930 AN XY: 74498

African (AFR) AF: 0.00469 AC: 195 AN: 41560

American (AMR) AF: 0.00850 AC: 130 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4828

European-Finnish (FIN) AF: 0.00367 AC: 39 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0244 AC: 1659 AN: 68038

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.0195 Hom.: 84

Bravo AF: 0.0139

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	0.019
DEOGEN2	Benign	0.0077	T
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0037	T
PhyloP100		-2.0
Sift4G	Benign	0.48	T
Vest4		0.048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.11

Splicing

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

Other links and lift over

dbSNP: rs203710; hg19: chr19-45162038;