rs139112266

Positions:

• chrX-13744539-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003611.3(OFD1):​c.517+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 909,326 control chromosomes in the GnomAD database, including 2 homozygotes. There are 84 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 0.0019 (1 hom., 52 hem., cov: 24)
  • Exomes 𝑓: 0.00022 (1 hom. 32 hem.)
• Consequence: OFD1 NM_003611.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0920

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-13744539-T-C is Benign according to our data. Variant chrX-13744539-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 259100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-13744539-T-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00193 (217/112487) while in subpopulation AFR AF= 0.00632 (196/31017). AF 95% confidence interval is 0.0056. There are 1 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 52 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OFD1	NM_003611.3	c.517+20T>C		intron_variant		ENST00000340096.11	NP_003602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OFD1	ENST00000340096.11	c.517+20T>C		intron_variant		1	NM_003611.3	ENSP00000344314.6

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 217 AN: 112432 Hom.: 1 Cov.: 24 AF XY: 0.00150 AC XY: 52 AN XY: 34578

Gnomad AFR AF: 0.00633

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

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: 0.0000188

Gnomad OTH AF: 0.00266

GnomAD3 exomes AF: 0.000567 AC: 100 AN: 176474 Hom.: 0 AF XY: 0.000356 AC XY: 22 AN XY: 61728

Gnomad AFR exome AF: 0.00660

Gnomad AMR exome AF: 0.000591

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000223 AC: 178 AN: 796839 Hom.: 1 Cov.: 14 AF XY: 0.000151 AC XY: 32 AN XY: 212521

Gnomad4 AFR exome AF: 0.00644

Gnomad4 AMR exome AF: 0.000606

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000210

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000352

Gnomad4 OTH exome AF: 0.000558

GnomAD4 genome AF: 0.00193 AC: 217 AN: 112487 Hom.: 1 Cov.: 24 AF XY: 0.00150 AC XY: 52 AN XY: 34643

Gnomad4 AFR AF: 0.00632

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00262

Alfa AF: 0.00117 Hom.: 7

Bravo AF: 0.00225

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 11, 2017	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. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.57
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

LitVar

Other links and lift over

dbSNP: rs139112266; hg19: chrX-13762658;