chrX-68335209-T-A

Variant names:

• chrX-68335209-T-A
• rs5965550
• NM_002547.3:c.155-36113A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002547.3(OPHN1):​c.155-36113A>T 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 0.33 (8037 hom., 9179 hem., cov: 20)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 2 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: Orphanet, ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.155-36113A>T		intron_variant	Intron 2 of 24	ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.155-36113A>T		intron_variant	Intron 2 of 24	1	NM_002547.3	ENSP00000347710.5

Frequencies

GnomAD3 genomes AF: 0.333 AC: 35704 AN: 107064 Hom.: 8025 Cov.: 20

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.198

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.334 AC: 35756 AN: 107082 Hom.: 8037 Cov.: 20 AF XY: 0.308 AC XY: 9179 AN XY: 29788

African (AFR) AF: 0.810 AC: 23632 AN: 29160

American (AMR) AF: 0.226 AC: 2241 AN: 9896

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 400 AN: 2621

East Asian (EAS) AF: 0.125 AC: 424 AN: 3385

South Asian (SAS) AF: 0.214 AC: 514 AN: 2399

European-Finnish (FIN) AF: 0.167 AC: 836 AN: 5010

Middle Eastern (MID) AF: 0.176 AC: 36 AN: 205

European-Non Finnish (NFE) AF: 0.136 AC: 7137 AN: 52300

Other (OTH) AF: 0.310 AC: 447 AN: 1440

Alfa AF: 0.230 Hom.: 1566

Bravo AF: 0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		0.34
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

Other links and lift over

dbSNP: rs5965550; hg19: chrX-67555051;