rs145300245

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003611.3(OFD1):​c.1923G>A​(p.Glu641Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00455 in 1,207,779 control chromosomes in the GnomAD database, including 9 homozygotes. There are 1,687 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., 80 hem., cov: 23)
Exomes 𝑓: 0.0047 ( 8 hom. 1607 hem. )

Consequence

OFD1
NM_003611.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 3.95
Variant links:
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant X-13760383-G-A is Benign according to our data. Variant chrX-13760383-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 41088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-13760383-G-A is described in Lovd as [Benign]. Variant chrX-13760383-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00291 (326/111975) while in subpopulation NFE AF= 0.00504 (268/53191). AF 95% confidence interval is 0.00454. There are 1 homozygotes in gnomad4. There are 80 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 80 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OFD1NM_003611.3 linkuse as main transcriptc.1923G>A p.Glu641Glu synonymous_variant 16/23 ENST00000340096.11 NP_003602.1 O75665-1E9KL37

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OFD1ENST00000340096.11 linkuse as main transcriptc.1923G>A p.Glu641Glu synonymous_variant 16/231 NM_003611.3 ENSP00000344314.6 O75665-1

Frequencies

GnomAD3 genomes
AF:
0.00291
AC:
326
AN:
111924
Hom.:
1
Cov.:
23
AF XY:
0.00235
AC XY:
80
AN XY:
34082
show subpopulations
Gnomad AFR
AF:
0.000390
Gnomad AMI
AF:
0.0293
Gnomad AMR
AF:
0.00132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00149
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00504
Gnomad OTH
AF:
0.00202
GnomAD3 exomes
AF:
0.00282
AC:
513
AN:
182056
Hom.:
2
AF XY:
0.00281
AC XY:
187
AN XY:
66622
show subpopulations
Gnomad AFR exome
AF:
0.000457
Gnomad AMR exome
AF:
0.000515
Gnomad ASJ exome
AF:
0.000136
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00113
Gnomad NFE exome
AF:
0.00573
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.00472
AC:
5169
AN:
1095804
Hom.:
8
Cov.:
32
AF XY:
0.00445
AC XY:
1607
AN XY:
361528
show subpopulations
Gnomad4 AFR exome
AF:
0.000533
Gnomad4 AMR exome
AF:
0.000543
Gnomad4 ASJ exome
AF:
0.000156
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00123
Gnomad4 NFE exome
AF:
0.00587
Gnomad4 OTH exome
AF:
0.00324
GnomAD4 genome
AF:
0.00291
AC:
326
AN:
111975
Hom.:
1
Cov.:
23
AF XY:
0.00234
AC XY:
80
AN XY:
34143
show subpopulations
Gnomad4 AFR
AF:
0.000389
Gnomad4 AMR
AF:
0.00132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00149
Gnomad4 NFE
AF:
0.00504
Gnomad4 OTH
AF:
0.00199
Alfa
AF:
0.00313
Hom.:
27
Bravo
AF:
0.00276
EpiCase
AF:
0.00464
EpiControl
AF:
0.00558

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMar 18, 2016- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Oct 21, 2013- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsOct 02, 2019- -
not provided Benign:4
Likely benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingGeneDxSep 20, 2018This variant is associated with the following publications: (PMID: 18546297) -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 07, 2017This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -
Retinitis pigmentosa 23;C1510460:Orofaciodigital syndrome I;C1846175:Simpson-Golabi-Behmel syndrome type 2;C2749019:Joubert syndrome 10 Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsAug 30, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
3.9
DANN
Benign
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145300245; hg19: chrX-13778502; COSMIC: COSV60797781; COSMIC: COSV60797781; API