rs373792491
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP3BP6BS2_Supporting
The NM_003611.3(OFD1):āc.1634A>Gā(p.Gln545Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000411 in 1,168,999 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000054 ( 0 hom., 2 hem., cov: 22)
Exomes š: 0.000040 ( 0 hom. 17 hem. )
Consequence
OFD1
NM_003611.3 missense
NM_003611.3 missense
Scores
6
5
6
Clinical Significance
Conservation
PhyloP100: 6.86
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_benign. Variant got -1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.767
BP6
?
Variant X-13758428-A-G is Benign according to our data. Variant chrX-13758428-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 447888.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS2
?
High Hemizygotes in GnomAd4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OFD1 | NM_003611.3 | c.1634A>G | p.Gln545Arg | missense_variant | 15/23 | ENST00000340096.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OFD1 | ENST00000340096.11 | c.1634A>G | p.Gln545Arg | missense_variant | 15/23 | 1 | NM_003611.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000536 AC: 6AN: 111894Hom.: 0 Cov.: 22 AF XY: 0.0000587 AC XY: 2AN XY: 34064
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GnomAD3 exomes AF: 0.0000493 AC: 9AN: 182633Hom.: 0 AF XY: 0.0000446 AC XY: 3AN XY: 67215
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GnomAD4 exome AF: 0.0000397 AC: 42AN: 1057105Hom.: 0 Cov.: 25 AF XY: 0.0000522 AC XY: 17AN XY: 325931
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GnomAD4 genome ? AF: 0.0000536 AC: 6AN: 111894Hom.: 0 Cov.: 22 AF XY: 0.0000587 AC XY: 2AN XY: 34064
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 04, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2020 | - - |
Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;T
Sift4G
Uncertain
D;T;T
Polyphen
D;D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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