rs201511311
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_032119.4(ADGRV1):c.9557C>A(p.Thr3186Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T3186T) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ADGRV1
NM_032119.4 missense
NM_032119.4 missense
Scores
3
4
6
Clinical Significance
Conservation
PhyloP100: 4.27
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 5-90720157-C-A is Benign according to our data. Variant chr5-90720157-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 505837.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.9557C>A | p.Thr3186Asn | missense_variant | 44/90 | ENST00000405460.9 | |
LOC105379077 | XR_001742802.2 | n.364-4348G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.9557C>A | p.Thr3186Asn | missense_variant | 44/90 | 1 | NM_032119.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247068Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134094
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458804Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725552
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GnomAD4 genome ? Cov.: 33
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?
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33
ExAC
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 31, 2017 | The p.Thr3186Asn variant in GPR98 has not been previously reported in individual s with hearing loss or Usher syndrome. This variant has been identified in 1/152 24 African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad .broadinstitute.org; dbSNP rs201511311). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogeni c role. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Thr3186Asn variant is uncertain. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
D;D
Vest4
0.85
MutPred
Loss of catalytic residue at T3186 (P = 0.1509);Loss of catalytic residue at T3186 (P = 0.1509);
MVP
0.75
MPC
0.32
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at