Variant 7-100220149-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001397246.1(PVRIG):c.94G>A(p.Ala32Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PVRIG
NM_001397246.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.210

Variant links:

Genes affected

PVRIG (HGNC:32190): (PVR related immunoglobulin domain containing) Enables phosphatase binding activity and signaling receptor activity. Involved in negative regulation of T cell receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PVRIG links:

CASTOR3P (HGNC:29954): (CASTOR family member 3, pseudogene) Predicted to be involved in cellular response to L-arginine and negative regulation of TORC1 signaling. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CASTOR3P links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2512641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVRIG	NM_001397246.1 linkuse as main transcript	c.94G>A	p.Ala32Thr	missense_variant	2/5	ENST00000699088.1
CASTOR3P	NR_028040.1 linkuse as main transcript	n.913+2448C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVRIG	ENST00000699088.1 linkuse as main transcript	c.94G>A	p.Ala32Thr	missense_variant	2/5		NM_001397246.1	A2
CASTOR3P	ENST00000649671.1 linkuse as main transcript	n.775+3421C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000447

AC:

AN:

223774

Hom.:

AF XY:

0.00000825

AC XY:

AN XY:

121188

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000588

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446190

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718378

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.154G>A (p.A52T) alteration is located in exon 3 (coding exon 2) of the PVRIG gene. This alteration results from a G to A substitution at nucleotide position 154, causing the alanine (A) at amino acid position 52 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.088

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.62

M_CAP

Benign

0.036

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.17

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.33

MutPred

0.35

Gain of catalytic residue at A52 (P = 0.0135);

MVP

0.63

MPC

0.43

ClinPred

0.73

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over