X-91877251-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032968.5(PCDH11X):c.1011A>G(p.Ala337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., 30 hem., cov: 14)
  • Exomes 𝑓: 0.00030 (1 hom. 57 hem.)
• Consequence: PCDH11X NM_032968.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.147

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-91877251-A-G is Benign according to our data. Variant chrX-91877251-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 724999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.147 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH11X	NM_032968.5	c.1011A>G	p.Ala337=	synonymous_variant	6/11	ENST00000682573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH11X	ENST00000682573.1	c.1011A>G	p.Ala337=	synonymous_variant	6/11		NM_032968.5	P4

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 201 AN: 91806 Hom.: 1 Cov.: 14 AF XY: 0.00186 AC XY: 32 AN XY: 17180

Gnomad AFR AF: 0.00782

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000383

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000431

Gnomad OTH AF: 0.00174

GnomAD3 exomes AF: 0.000783 AC: 81 AN: 103477 Hom.: 0 AF XY: 0.000397 AC XY: 11 AN XY: 27701

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000243

Gnomad OTH exome AF: 0.000665

GnomAD4 exome AF: 0.000297 AC: 291 AN: 981124 Hom.: 1 Cov.: 19 AF XY: 0.000199 AC XY: 57 AN XY: 286872

Gnomad4 AFR exome AF: 0.00979

Gnomad4 AMR exome AF: 0.000473

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000803

Gnomad4 OTH exome AF: 0.000783

GnomAD4 genome AF: 0.00219 AC: 201 AN: 91843 Hom.: 1 Cov.: 14 AF XY: 0.00174 AC XY: 30 AN XY: 17231

Gnomad4 AFR AF: 0.00780

Gnomad4 AMR AF: 0.000383

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000431

Gnomad4 OTH AF: 0.00172

Alfa AF: 0.00158 Hom.: 10

Bravo AF: 0.00287

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	2.0
Dann	Benign	0.27

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

LitVar

Other links and lift over

dbSNP: rs367906861; hg19: chrX-91132250;