X-13735162-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.756

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1235588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OFD1	NM_003611.3	c.12+79T>G		intron_variant		ENST00000340096.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OFD1	ENST00000340096.11	c.12+79T>G		intron_variant		1	NM_003611.3	P1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2052 AN: 112850 Hom.: 41 Cov.: 24 AF XY: 0.0157 AC XY: 548 AN XY: 35000

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

Gnomad4 AFR exome AF: 0.0664

Gnomad4 AMR exome AF: 0.00293

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000744

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000481

Gnomad4 OTH exome AF: 0.00342

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

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.00631

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000131

Gnomad4 OTH AF: 0.0182

Alfa AF: 0.0108 Hom.: 5

Bravo AF: 0.0211

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.5
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs141160969; hg19: chrX-13753281;