NM_002547.3:c.2056C>A

Variant names:

• chrX-68063956-G-T
• NM_002547.3:c.2056C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002547.3(OPHN1):​c.2056C>A​(p.Pro686Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,315 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: OPHN1 NM_002547.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.2056C>A	p.Pro686Thr	missense_variant	Exon 21 of 25	ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.2056C>A	p.Pro686Thr	missense_variant	Exon 21 of 25	1	NM_002547.3	ENSP00000347710.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096315 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 361793

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.2
DANN	Benign	0.18
DEOGEN2	Benign	0.039	T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.068
Sift	Benign	0.27	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.049
MutPred		0.20		Gain of phosphorylation at P686 (P = 0.0535);
MVP		0.15
MPC		0.13
ClinPred		0.058	T
GERP RS		-1.2
Varity_R		0.061
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-67283798;