chrX-92138738-A-G

Variant names:

• chrX-92138738-A-G
• rs5984894
• NM_032968.5:c.3034-62637A>G

Variant summary

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

The NM_032968.5(PCDH11X):​c.3034-62637A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 109,929 control chromosomes in the GnomAD database, including 12,273 homozygotes. There are 16,070 hemizygotes in GnomAD. 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 0.53 (12273 hom., 16070 hem., cov: 23)
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 30 publications found

Genes affected

PCDH11X (HGNC:8656): (protocadherin 11 X-linked) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

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 = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.3034-62637A>G		intron_variant	Intron 6 of 10	ENST00000682573.1	NP_116750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1	c.3034-62637A>G		intron_variant	Intron 6 of 10		NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 57985 AN: 109881 Hom.: 12280 Cov.: 23

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.451

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.528 AC: 58001 AN: 109929 Hom.: 12273 Cov.: 23 AF XY: 0.498 AC XY: 16070 AN XY: 32249

African (AFR) AF: 0.722 AC: 21904 AN: 30328

American (AMR) AF: 0.343 AC: 3499 AN: 10203

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 989 AN: 2643

East Asian (EAS) AF: 0.112 AC: 395 AN: 3520

South Asian (SAS) AF: 0.287 AC: 752 AN: 2622

European-Finnish (FIN) AF: 0.413 AC: 2328 AN: 5630

Middle Eastern (MID) AF: 0.459 AC: 94 AN: 205

European-Non Finnish (NFE) AF: 0.513 AC: 26977 AN: 52619

Other (OTH) AF: 0.488 AC: 728 AN: 1492

Alfa AF: 0.513 Hom.: 18401

Bravo AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.048
DANN	Benign	0.46
PhyloP100		-2.3
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: rs5984894; hg19: chrX-91393737;