rs376900429
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_032119.4(ADGRV1):c.3775T>A(p.Ser1259Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
ADGRV1
NM_032119.4 missense
NM_032119.4 missense
Scores
1
5
7
Clinical Significance
Conservation
PhyloP100: 5.90
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.33145955).
BP6
?
Variant 5-90653349-T-A is Benign according to our data. Variant chr5-90653349-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 46320.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.3775T>A | p.Ser1259Thr | missense_variant | 20/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.3775T>A | p.Ser1259Thr | missense_variant | 20/90 | 1 | NM_032119.4 | P1 | |
ADGRV1 | ENST00000640403.1 | c.1066T>A | p.Ser356Thr | missense_variant | 10/29 | 5 | |||
ADGRV1 | ENST00000504142.2 | n.2541T>A | non_coding_transcript_exon_variant | 14/14 | 5 | ||||
ADGRV1 | ENST00000639676.1 | n.1373T>A | non_coding_transcript_exon_variant | 8/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249132Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135140
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461694Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727126
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74322
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign: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 | Oct 17, 2011 | Variant classified as Uncertain Significance - Favor Benign. The Ser1259Thr vari ant in GPR98 has not been reported in the literature nor previously identified b y our laboratory. Although this residue is highly conserved across species and c omputational analyses (PolyPhen2, SIFT, AlignGVGD) suggest that the Ser1259Thr v ariant may impact the protein, this information is not predictive enough to assu me pathogenicity. In summary, the clinical significance of this variant cannot b e determined with certainty at this time. - |
Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
D;D;.
Vest4
0.45
MVP
0.59
MPC
0.14
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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