X-13761222-C-T

Variant names:

• chrX-13761222-C-T
• rs140369491
• NM_003611.3:c.2387+11C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.40
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 10

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• orofaciodigital syndrome I

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 23

  Inheritance: XL Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Simpson-Golabi-Behmel syndrome type 2

  Inheritance: XL Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 159471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003611.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OFD1	NM_003611.3	MANE Select	c.2387+11C>T		intron	N/A	NP_003602.1
	OFD1	NM_001440947.1		c.2387+11C>T		intron	N/A	NP_001427876.1
	OFD1	NM_001330209.2		c.2267+11C>T		intron	N/A	NP_001317138.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OFD1	ENST00000340096.11	TSL:1 MANE Select	c.2387+11C>T		intron	N/A	ENSP00000344314.6
	OFD1	ENST00000380550.6	TSL:1	c.2267+11C>T		intron	N/A	ENSP00000369923.3
	OFD1	ENST00000380567.6	TSL:5	n.*2080+11C>T		intron	N/A	ENSP00000369941.2

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 2473 AN: 110620 Hom.: 62 Cov.: 22

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

GnomAD2 exomes AF: 0.0133 AC: 2431 AN: 183349 AF XY: 0.0140

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 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.: 31 AF XY: 0.00688 AC XY: 2486 AN XY: 361254

African (AFR) AF: 0.0671 AC: 1768 AN: 26350

American (AMR) AF: 0.00600 AC: 211 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.000827 AC: 16 AN: 19356

East Asian (EAS) AF: 0.0292 AC: 882 AN: 30186

South Asian (SAS) AF: 0.0476 AC: 2573 AN: 54097

European-Finnish (FIN) AF: 0.0000494 AC: 2 AN: 40473

Middle Eastern (MID) AF: 0.00776 AC: 32 AN: 4125

European-Non Finnish (NFE) AF: 0.000452 AC: 380 AN: 840057

Other (OTH) AF: 0.0111 AC: 510 AN: 46023

GnomAD4 genome AF: 0.0224 AC: 2481 AN: 110674 Hom.: 61 Cov.: 22 AF XY: 0.0201 AC XY: 660 AN XY: 32896

African (AFR) AF: 0.0667 AC: 2027 AN: 30389

American (AMR) AF: 0.0155 AC: 160 AN: 10345

Ashkenazi Jewish (ASJ) AF: 0.00113 AC: 3 AN: 2645

East Asian (EAS) AF: 0.0226 AC: 79 AN: 3500

South Asian (SAS) AF: 0.0470 AC: 123 AN: 2616

European-Finnish (FIN) AF: 0.000173 AC: 1 AN: 5772

Middle Eastern (MID) AF: 0.0137 AC: 3 AN: 219

European-Non Finnish (NFE) AF: 0.000812 AC: 43 AN: 52986

Other (OTH) AF: 0.0277 AC: 42 AN: 1514

Alfa AF: 0.0110 Hom.: 58

Bravo AF: 0.0252

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Significance: Benign

Review Status: no assertion criteria provided

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.

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

Joubert syndrome;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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.012
DANN	Benign	0.54
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs140369491; hg19: chrX-13779341;