X-13735162-T-G

Variant names:

• chrX-13735162-T-G
• rs141160969
• NM_003611.3:c.12+79T>G

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.12+79T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,199,109 control chromosomes in the GnomAD database, including 82 homozygotes. There are 1,087 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (40 hom., 551 hem., cov: 24)
  • Exomes 𝑓: 0.0019 (42 hom. 536 hem.)
• Consequence: OFD1 NM_003611.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.756
• Publications: 0 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):

• Joubert syndrome 10

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• OFD1-related ciliopathy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.77).
• BP6: Variant X-13735162-T-G is Benign according to our data. Variant chrX-13735162-T-G is described in ClinVar as Benign. ClinVar VariationId is 1235588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0604 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OFD1	NM_003611.3	MANE Select	c.12+79T>G		intron	N/A	NP_003602.1	O75665-1
	OFD1	NM_001440947.1		c.12+79T>G		intron	N/A	NP_001427876.1
	OFD1	NM_001330209.2		c.12+79T>G		intron	N/A	NP_001317138.1	O75665-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OFD1	ENST00000340096.11	TSL:1 MANE Select	c.12+79T>G		intron	N/A	ENSP00000344314.6	O75665-1
	OFD1	ENST00000380550.6	TSL:1	c.12+79T>G		intron	N/A	ENSP00000369923.3	O75665-3
	OFD1	ENST00000922714.1		c.12+79T>G		intron	N/A	ENSP00000592773.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2052 AN: 112850 Hom.: 41 Cov.: 24

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00632

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: 0.000131

Gnomad OTH AF: 0.0184

GnomAD4 exome AF: 0.00189 AC: 2049 AN: 1086205 Hom.: 42 Cov.: 28 AF XY: 0.00152 AC XY: 536 AN XY: 352317

African (AFR) AF: 0.0664 AC: 1737 AN: 26146

American (AMR) AF: 0.00293 AC: 103 AN: 35132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19313

East Asian (EAS) AF: 0.00 AC: 0 AN: 30118

South Asian (SAS) AF: 0.0000744 AC: 4 AN: 53746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40278

Middle Eastern (MID) AF: 0.00219 AC: 9 AN: 4103

European-Non Finnish (NFE) AF: 0.0000481 AC: 40 AN: 831765

Other (OTH) AF: 0.00342 AC: 156 AN: 45604

GnomAD4 genome AF: 0.0182 AC: 2056 AN: 112904 Hom.: 40 Cov.: 24 AF XY: 0.0157 AC XY: 551 AN XY: 35064

African (AFR) AF: 0.0627 AC: 1953 AN: 31124

American (AMR) AF: 0.00631 AC: 68 AN: 10775

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3599

South Asian (SAS) AF: 0.00 AC: 0 AN: 2765

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000131 AC: 7 AN: 53300

Other (OTH) AF: 0.0182 AC: 28 AN: 1537

Alfa AF: 0.0108 Hom.: 5

Bravo AF: 0.0211

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.76
PromoterAI		-0.080	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141160969; hg19: chrX-13753281;