chrX-13753457-A-G

Position:

chrX-13753457-A-G

Variant summary

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

The ENST00000340096.11(OFD1):c.1129+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,203,519 control chromosomes in the GnomAD database, including 34,154 homozygotes. There are 110,867 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 3488 hom., 9543 hem., cov: 22)

Exomes 𝑓: 0.28 ( 30666 hom. 101324 hem. )

Consequence

OFD1
ENST00000340096.11 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -3.56

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=-0.97).

BP6

Variant X-13753457-A-G is Benign according to our data. Variant chrX-13753457-A-G is described in ClinVar as [Benign]. Clinvar id is 94370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-13753457-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OFD1	NM_003611.3 linkuse as main transcript	c.1129+16A>G		intron_variant		ENST00000340096.11	NP_003602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OFD1	ENST00000340096.11 linkuse as main transcript	c.1129+16A>G		intron_variant		1	NM_003611.3	ENSP00000344314	P1	O75665-1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

31892

AN:

110845

Hom.:

3480

Cov.:

AF XY:

0.288

AC XY:

9522

AN XY:

33103

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.300

GnomAD3 exomes

AF:

0.348

AC:

63613

AN:

182729

Hom.:

8855

AF XY:

0.339

AC XY:

22770

AN XY:

67253

show subpopulations

Gnomad AFR exome

AF:

0.280

Gnomad AMR exome

AF:

0.650

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.450

Gnomad SAS exome

AF:

0.466

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.277

AC:

302121

AN:

1092621

Hom.:

30666

Cov.:

AF XY:

0.282

AC XY:

101324

AN XY:

358671

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.624

Gnomad4 ASJ exome

AF:

0.248

Gnomad4 EAS exome

AF:

0.444

Gnomad4 SAS exome

AF:

0.464

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.288

AC:

31918

AN:

110898

Hom.:

3488

Cov.:

AF XY:

0.288

AC XY:

9543

AN XY:

33166

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.467

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.266

Hom.:

2736

Bravo

AF:

0.312

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 03, 2012	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Orofaciodigital syndrome I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Simpson-Golabi-Behmel syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Joubert syndrome 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Retinitis pigmentosa 23

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.16

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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