5-90647666-A-G

Variant summary

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

The NM_032119.4(ADGRV1):c.3191A>G(p.Glu1064Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1064A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

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=0.23529255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.3191A>G	p.Glu1064Gly	missense_variant	17/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.3191A>G	p.Glu1064Gly	missense_variant	17/90	1	NM_032119.4	P1
ADGRV1	ENST00000640403.1	c.494A>G	p.Glu165Gly	missense_variant	7/29	5
ADGRV1	ENST00000504142.2	n.1957A>G		non_coding_transcript_exon_variant	11/14	5
ADGRV1	ENST00000639676.1	n.789A>G		non_coding_transcript_exon_variant	5/11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	14
Dann	Uncertain	1.0
DEOGEN2	Benign	0.072	T;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.78	N
PrimateAI	Benign	0.27	T
Polyphen		0.15	B;B;.
Vest4		0.076
MutPred		0.48		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);.;
MVP		0.45
MPC		0.057
ClinPred		0.57	D
GERP RS		3.3
Varity_R		0.098
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs190922596; hg19: chr5-89943483;