rs267606933

Positions:

• chrX-100406927-G-A
• chrX-100406927-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001184880.2(PCDH19):​c.1671C>T​(p.Asn557Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,076 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: PCDH19 NM_001184880.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

Genes affected

PCDH19 (HGNC:14270): (protocadherin 19) The protein encoded by this gene is a member of the delta-2 protocadherin subclass of the cadherin superfamily. The encoded protein is thought to be a calcium-dependent cell-adhesion protein that is primarily expressed in the brain. Mutations in this gene on human chromosome X are associated with sporadic infantile epileptic encephalopathy and to a female-restricted form of epilepsy (EFMR; also known as PCDH19RE). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.089 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH19	NM_001184880.2	c.1671C>T	p.Asn557Asn	synonymous_variant	1/6	ENST00000373034.8	NP_001171809.1
PCDH19	NM_001105243.2	c.1671C>T	p.Asn557Asn	synonymous_variant	1/5		NP_001098713.1
PCDH19	NM_020766.3	c.1671C>T	p.Asn557Asn	synonymous_variant	1/5		NP_065817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH19	ENST00000373034.8	c.1671C>T	p.Asn557Asn	synonymous_variant	1/6	1	NM_001184880.2	ENSP00000362125.4
PCDH19	ENST00000255531.8	c.1671C>T	p.Asn557Asn	synonymous_variant	1/5	1		ENSP00000255531.7
PCDH19	ENST00000420881.6	c.1671C>T	p.Asn557Asn	synonymous_variant	1/5	1		ENSP00000400327.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098076 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363434

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.1
DANN	Benign	0.78

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: rs267606933; hg19: chrX-99661925; COSMIC: COSV55269259; COSMIC: COSV55269259;