rs138926050

Variant names:

• chrX-91835514-T-C
• rs138926050
• NM_032968.5:c.10T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032968.5(PCDH11X):​c.10T>C​(p.Leu4Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,209,426 control chromosomes in the GnomAD database, including 11 homozygotes. There are 332 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (7 hom., 169 hem., cov: 21)
  • Exomes 𝑓: 0.00055 (4 hom. 163 hem.)
• Consequence: PCDH11X NM_032968.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.06
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-91835514-T-C is Benign according to our data. Variant chrX-91835514-T-C is described in ClinVar as [Benign]. Clinvar id is 713259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00564 (627/111211) while in subpopulation AFR AF = 0.0199 (607/30562). AF 95% confidence interval is 0.0186. There are 7 homozygotes in GnomAd4. There are 169 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.10T>C	p.Leu4Leu	synonymous_variant	Exon 5 of 11	ENST00000682573.1	NP_116750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1	c.10T>C	p.Leu4Leu	synonymous_variant	Exon 5 of 11		NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes AF: 0.00564 AC: 627 AN: 111159 Hom.: 7 Cov.: 21

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00126

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000386

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000565

Gnomad OTH AF: 0.00202

GnomAD2 exomes AF: 0.00152 AC: 278 AN: 183468 AF XY: 0.00110

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.000840

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000488

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000550 AC: 604 AN: 1098215 Hom.: 4 Cov.: 31 AF XY: 0.000448 AC XY: 163 AN XY: 363591

African (AFR) AF: 0.0190 AC: 501 AN: 26396

American (AMR) AF: 0.000909 AC: 32 AN: 35192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00121 AC: 5 AN: 4137

European-Non Finnish (NFE) AF: 0.0000154 AC: 13 AN: 842122

Other (OTH) AF: 0.00115 AC: 53 AN: 46096

GnomAD4 genome AF: 0.00564 AC: 627 AN: 111211 Hom.: 7 Cov.: 21 AF XY: 0.00506 AC XY: 169 AN XY: 33385

African (AFR) AF: 0.0199 AC: 607 AN: 30562

American (AMR) AF: 0.00126 AC: 13 AN: 10351

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3529

South Asian (SAS) AF: 0.000388 AC: 1 AN: 2580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6041

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53099

Other (OTH) AF: 0.00199 AC: 3 AN: 1507

Alfa AF: 0.00874 Hom.: 72

Bravo AF: 0.00651

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.8
DANN	Benign	0.59
PhyloP100		3.1
PromoterAI		0.0058	Neutral
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: rs138926050; hg19: chrX-91090513;