5-90675436-G-T

Variant summary

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

The NM_032119.4(ADGRV1):c.5304G>T(p.Glu1768Asp) 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. E1768K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

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=0.17862356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.5304G>T	p.Glu1768Asp	missense_variant	24/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.5304G>T	p.Glu1768Asp	missense_variant	24/90	1	NM_032119.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	15
Dann	Uncertain	0.98
DEOGEN2	Benign	0.073	T;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.47	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.78	N
PrimateAI	Benign	0.24	T
Polyphen		0.0030	B;B;.
Vest4		0.15
MutPred		0.29		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);.;
MVP		0.26
MPC		0.067
ClinPred		0.16	T
GERP RS		0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.34

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: rs41303346; hg19: chr5-89971253;