Variant X-100296331-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001184880.2(PCDH19):c.3393A>G(p.Glu1131Glu) 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 1,098,045 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. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

PCDH19
NM_001184880.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.510

Variant links:

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]

PCDH19 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-100296331-T-C is Benign according to our data. Variant chrX-100296331-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1635447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.51 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH19	NM_001184880.2 link	c.3393A>G	p.Glu1131Glu	synonymous_variant	Exon 6 of 6	ENST00000373034.8	NP_001171809.1	Q8TAB3-1
PCDH19	NM_001105243.2 link	c.3252A>G	p.Glu1084Glu	synonymous_variant	Exon 5 of 5		NP_001098713.1	Q8TAB3-2B3KU71
PCDH19	NM_020766.3 link	c.3249A>G	p.Glu1083Glu	synonymous_variant	Exon 5 of 5		NP_065817.2	Q8TAB3-3B3KU71

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCDH19	ENST00000373034.8 link	c.3393A>G	p.Glu1131Glu	synonymous_variant	Exon 6 of 6	1	NM_001184880.2	ENSP00000362125.4	Q8TAB3-1
PCDH19	ENST00000255531.8 link	c.3252A>G	p.Glu1084Glu	synonymous_variant	Exon 5 of 5	1		ENSP00000255531.7	Q8TAB3-2
PCDH19	ENST00000420881.6 link	c.3249A>G	p.Glu1083Glu	synonymous_variant	Exon 5 of 5	1		ENSP00000400327.2	Q8TAB3-3
PCDH19	ENST00000464981.1 link	n.-31A>G		upstream_gene_variant		3		ENSP00000479805.1	A0A1Y8EN23

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000551

AC:

AN:

181631

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67553

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098045

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363407

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Developmental and epileptic encephalopathy, 9

Benign:1

Dec 27, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.7

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over