X-68052289-CAAAA-CA

Variant names:

• chrX-68052289-CAAA-C
• rs72307579
• NM_002547.3:c.2375+248_2375+250delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002547.3(OPHN1):​c.2375+248_2375+250delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000049 (0 hom., 0 hem., cov: 0)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

Genes affected

OPHN1 (HGNC:8148): (oligophrenin 1) This gene encodes a Rho-GTPase-activating protein that promotes GTP hydrolysis of Rho subfamily members. Rho proteins are important mediators of intracellular signal transduction, which affects cell migration and cell morphogenesis. Mutations in this gene are responsible for OPHN1-related X-linked cognitive disability with cerebellar hypoplasia and distinctive facial dysmorhphism. [provided by RefSeq, Jul 2008]

OPHN1 Gene-Disease associations (from GenCC):

• X-linked intellectual disability-cerebellar hypoplasia syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002547.3. 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
	OPHN1	NM_002547.3	MANE Select	c.2375+248_2375+250delTTT		intron	N/A	NP_002538.1	O60890-1
	OPHN1	NM_001437258.1		c.2051+248_2051+250delTTT		intron	N/A	NP_001424187.1	A0A7P0Z4E9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	ENST00000355520.6	TSL:1 MANE Select	c.2375+248_2375+250delTTT		intron	N/A	ENSP00000347710.5	O60890-1
	OPHN1	ENST00000905069.1		c.2375+248_2375+250delTTT		intron	N/A	ENSP00000575128.1
	OPHN1	ENST00000681408.1		c.2270+248_2270+250delTTT		intron	N/A	ENSP00000506619.1	A0A7P0TBH4

Frequencies

GnomAD3 genomes AF: 0.0000490 AC: 3 AN: 61242 Hom.: 0 Cov.: 0

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: 0.000696

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000654

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000490 AC: 3 AN: 61242 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8000

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18746

American (AMR) AF: 0.00 AC: 0 AN: 4869

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1570

East Asian (EAS) AF: 0.00 AC: 0 AN: 1775

South Asian (SAS) AF: 0.00 AC: 0 AN: 932

European-Finnish (FIN) AF: 0.000696 AC: 1 AN: 1437

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 115

European-Non Finnish (NFE) AF: 0.0000654 AC: 2 AN: 30601

Other (OTH) AF: 0.00 AC: 0 AN: 779

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs72307579; hg19: chrX-67272131;