rs876657825

Variant names:

• chr5-90651684-G-A
• rs876657825
• NM_032119.4:c.3370G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90651684-G-A
• chr5-90651684-G-C

Variant summary

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

The NM_032119.4(ADGRV1):​c.3370G>A​(p.Glu1124Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.3370G>A	p.Glu1124Lys	missense_variant	Exon 18 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.3370G>A	p.Glu1124Lys	missense_variant	Exon 18 of 90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000640403.1	c.673G>A	p.Glu225Lys	missense_variant	Exon 8 of 29	5		ENSP00000492531.1
ADGRV1	ENST00000504142.2	n.2136G>A		non_coding_transcript_exon_variant	Exon 12 of 14	5
ADGRV1	ENST00000639676.1	n.968G>A		non_coding_transcript_exon_variant	Exon 6 of 11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Glu1124Lys variant in GPR98 has not been previously reported in individual s with hearing loss or Usher syndrome and was absent from large population studi es. Computational prediction tools and conservation analysis suggest that this v ariant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Glu11 24Lys variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Pathogenic	0.41	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Uncertain	-0.24	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	.;N;.
REVEL	Benign	0.25
Sift	Uncertain	0.020	.;D;.
Sift4G	Uncertain	0.010	.;D;.
Polyphen		1.0	D;D;.
Vest4		0.83
MutPred		0.51		Gain of ubiquitination at E1124 (P = 0.0146);Gain of ubiquitination at E1124 (P = 0.0146);.;
MVP		0.63
MPC		0.20
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.45
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs876657825; hg19: chr5-89947501;