X-13736586-T-TTAAAAGAGCTGC
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM4PP5_Moderate
The NM_003611.3(OFD1):c.220_221insTAAAAGAGCTGC(p.Ser74delinsLeuLysGluLeuPro) variant causes a protein altering change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
OFD1
NM_003611.3 protein_altering
NM_003611.3 protein_altering
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.71
Genes affected
OFD1 (HGNC:2567): (OFD1 centriole and centriolar satellite protein) This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Many pseudogenes have been identified; a single pseudogene is found on chromosome 5 while as many as fifteen have been found on the Y chromosome. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_003611.3
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_003611.3.
PP5
Variant X-13736586-T-TTAAAAGAGCTGC is Pathogenic according to our data. Variant chrX-13736586-T-TTAAAAGAGCTGC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 559929.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OFD1 | NM_003611.3 | c.220_221insTAAAAGAGCTGC | p.Ser74delinsLeuLysGluLeuPro | protein_altering_variant | 3/23 | ENST00000340096.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OFD1 | ENST00000340096.11 | c.220_221insTAAAAGAGCTGC | p.Ser74delinsLeuLysGluLeuPro | protein_altering_variant | 3/23 | 1 | NM_003611.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Orofaciodigital syndrome I Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Aug 03, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at