X-13761222-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003611.3(OFD1):c.2387+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00734 in 1,206,536 control chromosomes in the GnomAD database, including 173 homozygotes. There are 3,146 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 61 hom., 660 hem., cov: 22)

Exomes 𝑓: 0.0058 ( 112 hom. 2486 hem. )

Consequence

OFD1
NM_003611.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.40

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]

OFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant X-13761222-C-T is Benign according to our data. Variant chrX-13761222-C-T is described in ClinVar as [Benign]. Clinvar id is 159471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-13761222-C-T is described in Lovd as [Likely_benign]. Variant chrX-13761222-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OFD1	NM_003611.3 link	c.2387+11C>T		intron_variant	Intron 17 of 22	ENST00000340096.11	NP_003602.1	O75665-1E9KL37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OFD1	ENST00000340096.11 link	c.2387+11C>T		intron_variant	Intron 17 of 22	1	NM_003611.3	ENSP00000344314.6		O75665-1

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

2473

AN:

110620

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

655

AN XY:

32832

show subpopulations

Gnomad AFR

AF:

0.0666

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.0225

Gnomad SAS

AF:

0.0481

Gnomad FIN

AF:

0.000173

Gnomad MID

AF:

0.0125

Gnomad NFE

AF:

0.000811

Gnomad OTH

AF:

0.0261

GnomAD3 exomes

AF:

0.0133

AC:

2431

AN:

183349

Hom.:

AF XY:

0.0140

AC XY:

946

AN XY:

67789

show subpopulations

Gnomad AFR exome

AF:

0.0699

Gnomad AMR exome

AF:

0.00441

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.0222

Gnomad SAS exome

AF:

0.0502

Gnomad FIN exome

AF:

0.0000627

Gnomad NFE exome

AF:

0.000843

Gnomad OTH exome

AF:

0.0102

GnomAD4 exome

AF:

0.00582

AC:

6374

AN:

1095862

Hom.:

112

Cov.:

AF XY:

0.00688

AC XY:

2486

AN XY:

361254

show subpopulations

Gnomad4 AFR exome

AF:

0.0671

Gnomad4 AMR exome

AF:

0.00600

Gnomad4 ASJ exome

AF:

0.000827

Gnomad4 EAS exome

AF:

0.0292

Gnomad4 SAS exome

AF:

0.0476

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.000452

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.0224

AC:

2481

AN:

110674

Hom.:

Cov.:

AF XY:

0.0201

AC XY:

660

AN XY:

32896

show subpopulations

Gnomad4 AFR

AF:

0.0667

Gnomad4 AMR

AF:

0.0155

Gnomad4 ASJ

AF:

0.00113

Gnomad4 EAS

AF:

0.0226

Gnomad4 SAS

AF:

0.0470

Gnomad4 FIN

AF:

0.000173

Gnomad4 NFE

AF:

0.000812

Gnomad4 OTH

AF:

0.0277

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.0252

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 31, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.012

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over