NM_003611.3:c.282C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_003611.3(OFD1):c.282C>T(p.Phe94Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,207,344 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 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 0.000054 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. 4 hem. )

Consequence

OFD1
NM_003611.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.44

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant X-13736648-C-T is Benign according to our data. Variant chrX-13736648-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 412873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.44 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 3 XL,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OFD1	NM_003611.3 link	c.282C>T	p.Phe94Phe	synonymous_variant	Exon 3 of 23	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.282C>T	p.Phe94Phe	synonymous_variant	Exon 3 of 23	1	NM_003611.3	ENSP00000344314.6		O75665-1

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111171

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000218

AC:

AN:

183378

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000489

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1096173

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

361577

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26376

American (AMR)

AF:

0.00

AC:

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19374

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.00

AC:

AN:

54085

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4099

European-Non Finnish (NFE)

AF:

0.0000143

AC:

AN:

840295

Other (OTH)

AF:

0.0000217

AC:

AN:

46025

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000540

AC:

AN:

111171

Hom.:

Cov.:

AF XY:

0.0000899

AC XY:

AN XY:

33355

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30563

American (AMR)

AF:

0.00

AC:

AN:

10470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3547

South Asian (SAS)

AF:

0.00

AC:

AN:

2608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53005

Other (OTH)

AF:

0.00

AC:

AN:

1490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome;C1510460:Orofaciodigital syndrome I

Benign:1

Apr 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 23;C1510460:Orofaciodigital syndrome I;C1846175:Simpson-Golabi-Behmel syndrome type 2;C2749019:Joubert syndrome 10

Benign:1

Nov 17, 2021

Fulgent Genetics, Fulgent Genetics

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

-0.33

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

2.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over