Genetic Variant NM_003611.3:c.12+79T>C (chrX-13735162-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003611.3(OFD1):c.12+79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,199,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000029 ( 0 hom. 14 hem. )

Consequence

OFD1
NM_003611.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.756

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BS2

High Hemizygotes in GnomAdExome4 at 14 XL,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OFD1	NM_003611.3 link	c.12+79T>C		intron_variant	Intron 1 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.12+79T>C		intron_variant	Intron 1 of 22	1	NM_003611.3	ENSP00000344314.6		O75665-1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000929

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000295

AC:

AN:

1086206

Hom.:

Cov.:

AF XY:

0.0000397

AC XY:

AN XY:

352318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26146

American (AMR)

AF:

0.00

AC:

AN:

35133

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19313

East Asian (EAS)

AF:

0.00

AC:

AN:

30118

South Asian (SAS)

AF:

0.00

AC:

AN:

53746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4103

European-Non Finnish (NFE)

AF:

0.0000361

AC:

AN:

831765

Other (OTH)

AF:

0.0000439

AC:

AN:

45604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000266

AC:

AN:

112854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35004

show subpopulations

African (AFR)

AF:

0.0000644

AC:

AN:

31060

American (AMR)

AF:

0.0000929

AC:

AN:

10762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3610

South Asian (SAS)

AF:

0.00

AC:

AN:

2773

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53306

Other (OTH)

AF:

0.00

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.7

(source)

DANN

Benign

0.49

PhyloP100

-0.76

PromoterAI

0.056

Neutral

(source)

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

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NM_003611.3:c.12+79T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over