7-100219969-C-G

Position:

• chr7-100219969-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024070.3(PVRIG):​c.59C>G​(p.Ala20Gly) 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. 14/23 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)
• Consequence: PVRIG NM_024070.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.343

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]

ENSG00000292277 (HGNC:):

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]

ACMG classification

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=0.15654999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVRIG	NM_001397246.1	c.-2C>G		5_prime_UTR_variant	1/5	ENST00000699088.1	NP_001384175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVRIG	ENST00000699088	c.-2C>G		5_prime_UTR_variant	1/5		NM_001397246.1	ENSP00000514123.1
ENSG00000292277	ENST00000710637.1	n.*1296C>G		non_coding_transcript_exon_variant	6/9			ENSP00000518392.1
ENSG00000292277	ENST00000710637.1	n.*1296C>G		3_prime_UTR_variant	6/9			ENSP00000518392.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.59C>G (p.A20G) alteration is located in exon 2 (coding exon 1) of the PVRIG gene. This alteration results from a C to G substitution at nucleotide position 59, causing the alanine (A) at amino acid position 20 to be replaced by a glycine (G). 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	0.097
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.043
Sift	Benign	0.054	T
Sift4G	Benign	0.061	T
Polyphen		0.99	D
Vest4		0.12
MutPred		0.26		Gain of sheet (P = 0.0477);
MVP		0.40
MPC		0.44
ClinPred		0.25	T
GERP RS		0.92
Varity_R		0.091
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99817592;