rs1555941116
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_004312.3(ARR3):c.239T>C(p.Leu80Pro) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 22)
Consequence
ARR3
NM_004312.3 missense
NM_004312.3 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 0.645
Genes affected
ARR3 (HGNC:710): (arrestin 3) The protein encoded by this gene is a non-visual arrestin which binds to agonist-activated, phosphorylated G protein-coupled receptors. This binding uncouples the receptor from the heterotrimeric G protein, resulting in termination of the G protein-coupled receptor signaling. The encoded protein also is a part of the centrosome, interacting with gamma-tubulin to help regulate proper centrosome function. [provided by RefSeq, May 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-70276175-T-C is Pathogenic according to our data. Variant chrX-70276175-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 478826.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-70276175-T-C is described in Lovd as [Pathogenic].
BP4
?
Computational evidence support a benign effect (MetaRNN=0.20372704). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARR3 | NM_004312.3 | c.239T>C | p.Leu80Pro | missense_variant | 6/17 | ENST00000307959.9 | |
ARR3 | XM_047442105.1 | c.263T>C | p.Leu88Pro | missense_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARR3 | ENST00000307959.9 | c.239T>C | p.Leu80Pro | missense_variant | 6/17 | 1 | NM_004312.3 | P1 | |
ARR3 | ENST00000374495.7 | c.239T>C | p.Leu80Pro | missense_variant | 6/16 | 1 | |||
ARR3 | ENST00000480877.6 | c.86T>C | p.Leu29Pro | missense_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Myopia 26, X-linked, female-limited Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 22, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;N;D
REVEL
Benign
Sift
Benign
T;.;T;T
Sift4G
Benign
T;T;T;T
Polyphen
P;.;.;P
Vest4
MutPred
Gain of disorder (P = 0.0154);Gain of disorder (P = 0.0154);.;Gain of disorder (P = 0.0154);
MVP
MPC
0.20
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at