X-13758318-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003611.3(OFD1):c.1543-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000567 in 1,049,732 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 180 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., 13 hem., cov: 22)

Exomes 𝑓: 0.00059 ( 0 hom. 167 hem. )

Consequence

OFD1
NM_003611.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.687

Publications

0 publications found

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 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

OFD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-13758318-C-G is Benign according to our data. Variant chrX-13758318-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 259095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 13 XL,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OFD1	NM_003611.3 link	c.1543-19C>G		intron_variant	Intron 14 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.1543-19C>G		intron_variant	Intron 14 of 22	1	NM_003611.3	ENSP00000344314.6		O75665-1

Frequencies

GnomAD3 genomes

AF:

0.000413

AC:

AN:

111256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000480

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000715

Gnomad OTH

AF:

0.000672

GnomAD2 exomes

AF:

0.000312

AC:

AN:

179539

AF XY:

0.000326

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000547

Gnomad OTH exome

AF:

0.000451

GnomAD4 exome

AF:

0.000585

AC:

549

AN:

938421

Hom.:

Cov.:

AF XY:

0.000628

AC XY:

167

AN XY:

265769

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23295

American (AMR)

AF:

0.000374

AC:

AN:

34731

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18339

East Asian (EAS)

AF:

0.00

AC:

AN:

29452

South Asian (SAS)

AF:

0.00

AC:

AN:

50142

European-Finnish (FIN)

AF:

0.0000248

AC:

AN:

40381

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3663

European-Non Finnish (NFE)

AF:

0.000741

AC:

517

AN:

697694

Other (OTH)

AF:

0.000442

AC:

AN:

40724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000413

AC:

AN:

111311

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

AN XY:

33513

show subpopulations

African (AFR)

AF:

0.0000652

AC:

AN:

30680

American (AMR)

AF:

0.000479

AC:

AN:

10439

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3554

South Asian (SAS)

AF:

0.00

AC:

AN:

2670

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000715

AC:

AN:

53111

Other (OTH)

AF:

0.000664

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000695

Hom.:

Bravo

AF:

0.000480

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome;C1510460:Orofaciodigital syndrome I

Benign:1

Dec 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 09, 2020

GeneDx

Significance:Likely 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

-0.79

CADD

Benign

7.3

(source)

DANN

Benign

0.64

PhyloP100

0.69

BranchPoint Hunter

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-13758318-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over