rs1057518963
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_002547.3(OPHN1):c.746T>C(p.Leu249Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 22)
Consequence
OPHN1
NM_002547.3 missense
NM_002547.3 missense
Scores
6
8
3
Clinical Significance
Conservation
PhyloP100: 8.25
Genes affected
OPHN1 (HGNC:8148): (oligophrenin 1) This gene encodes a Rho-GTPase-activating protein that promotes GTP hydrolysis of Rho subfamily members. Rho proteins are important mediators of intracellular signal transduction, which affects cell migration and cell morphogenesis. Mutations in this gene are responsible for OPHN1-related X-linked cognitive disability with cerebellar hypoplasia and distinctive facial dysmorhphism. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.827
PP5
?
Variant X-68210239-A-G is Pathogenic according to our data. Variant chrX-68210239-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 374192.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-68210239-A-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPHN1 | NM_002547.3 | c.746T>C | p.Leu249Pro | missense_variant | 9/25 | ENST00000355520.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPHN1 | ENST00000355520.6 | c.746T>C | p.Leu249Pro | missense_variant | 9/25 | 1 | NM_002547.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nystagmus;C0036572:Seizure;C0079924:Oligohydramnios;C0344482:Hypoplasia of the corpus callosum;C1837658:Delayed gross motor development;C5231391:Congenital cerebellar hypoplasia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jun 06, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of glycosylation at L249 (P = 0.0162);
MVP
MPC
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