X-68101899-G-T

Variant names:

• chrX-68101899-G-T
• rs1157321
• NM_002547.3:c.1527-4870C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002547.3(OPHN1):​c.1527-4870C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.77 (23143 hom., 25797 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 1 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]

RNU6-1225P (HGNC:48188): (RNA, U6 small nuclear 1225, pseudogene)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

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.1527-4870C>A		intron	N/A	NP_002538.1	O60890-1
	OPHN1	NM_001437258.1		c.1527-4870C>A		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.1527-4870C>A		intron	N/A	ENSP00000347710.5	O60890-1
	OPHN1	ENST00000905069.1		c.1527-4870C>A		intron	N/A	ENSP00000575128.1
	OPHN1	ENST00000681408.1		c.1422-4870C>A		intron	N/A	ENSP00000506619.1	A0A7P0TBH4

Frequencies

GnomAD3 genomes AF: 0.771 AC: 85539 AN: 110918 Hom.: 23149 Cov.: 24

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.762

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.771 AC: 85582 AN: 110970 Hom.: 23143 Cov.: 24 AF XY: 0.777 AC XY: 25797 AN XY: 33180

African (AFR) AF: 0.800 AC: 24467 AN: 30566

American (AMR) AF: 0.826 AC: 8628 AN: 10440

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 1873 AN: 2637

East Asian (EAS) AF: 0.996 AC: 3503 AN: 3518

South Asian (SAS) AF: 0.894 AC: 2367 AN: 2648

European-Finnish (FIN) AF: 0.771 AC: 4540 AN: 5886

Middle Eastern (MID) AF: 0.668 AC: 143 AN: 214

European-Non Finnish (NFE) AF: 0.728 AC: 38518 AN: 52875

Other (OTH) AF: 0.765 AC: 1158 AN: 1513

Alfa AF: 0.758 Hom.: 6291

Bravo AF: 0.780

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		0.069
Mutation Taster		=100/0	polymorphism (auto)

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: rs1157321; hg19: chrX-67321741;