rs183319660

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032119.4(ADGRV1):​c.10768A>C​(p.Ser3590Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense, splice_region

Scores

1
4
13
Splicing: ADA: 0.4186
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50
Variant links:
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=0.24361628).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADGRV1NM_032119.4 linkc.10768A>C p.Ser3590Arg missense_variant, splice_region_variant Exon 51 of 90 ENST00000405460.9 NP_115495.3 Q8WXG9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADGRV1ENST00000405460.9 linkc.10768A>C p.Ser3590Arg missense_variant, splice_region_variant Exon 51 of 90 1 NM_032119.4 ENSP00000384582.2 Q8WXG9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.06e-7
AC:
1
AN:
1415646
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
702498
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.59
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;T
Eigen
Benign
0.037
Eigen_PC
Benign
-0.025
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.81
.;T
M_CAP
Uncertain
0.086
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-2.0
.;N
REVEL
Benign
0.17
Sift
Benign
0.077
.;T
Sift4G
Uncertain
0.0030
.;D
Polyphen
0.97
D;D
Vest4
0.72
MutPred
0.29
Loss of phosphorylation at S3590 (P = 0.0452);Loss of phosphorylation at S3590 (P = 0.0452);
MVP
0.57
MPC
0.34
ClinPred
0.95
D
GERP RS
3.1
Varity_R
0.18
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.42
dbscSNV1_RF
Benign
0.61
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-90041081; API