X-23334968-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_173495.3(PTCHD1):c.93G>A(p.Ala31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 1,207,082 control chromosomes in the GnomAD database, including 346 homozygotes. There are 9,243 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 92 hom., 984 hem., cov: 22)

Exomes 𝑓: 0.022 ( 254 hom. 8259 hem. )

Consequence

PTCHD1
NM_173495.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.851

Variant links:

Genes affected

PTCHD1 (HGNC:26392): (patched domain containing 1) This gene encodes a membrane protein with a patched domain. The encoded protein is similar to Drosophila proteins which act as receptors for the morphogen sonic hedgehog. Deletions in this gene, which is located on the X chromosome, are associated with intellectual disability and autism (PMID: 21091464, PMID: 20844286). [provided by RefSeq, Aug 2011]

PTCHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant X-23334968-G-A is Benign according to our data. Variant chrX-23334968-G-A is described in ClinVar as [Benign]. Clinvar id is 96547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-23334968-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD1	NM_173495.3 linkuse as main transcript	c.93G>A	p.Ala31=	synonymous_variant	1/3	ENST00000379361.5
PTCHD1	XM_011545449.4 linkuse as main transcript	c.93G>A	p.Ala31=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCHD1	ENST00000379361.5 linkuse as main transcript	c.93G>A	p.Ala31=	synonymous_variant	1/3	1	NM_173495.3	P1	Q96NR3-1

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

3777

AN:

110686

Hom.:

Cov.:

AF XY:

0.0298

AC XY:

983

AN XY:

32952

show subpopulations

Gnomad AFR

AF:

0.0718

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0596

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0381

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.0508

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0352

GnomAD3 exomes

AF:

0.0230

AC:

4010

AN:

174527

Hom.:

AF XY:

0.0239

AC XY:

1480

AN XY:

61995

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.00912

Gnomad ASJ exome

AF:

0.0507

Gnomad EAS exome

AF:

0.0000756

Gnomad SAS exome

AF:

0.0424

Gnomad FIN exome

AF:

0.00493

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0242

GnomAD4 exome

AF:

0.0217

AC:

23794

AN:

1096355

Hom.:

254

Cov.:

AF XY:

0.0228

AC XY:

8259

AN XY:

361997

show subpopulations

Gnomad4 AFR exome

AF:

0.0780

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.0536

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.0430

Gnomad4 FIN exome

AF:

0.00569

Gnomad4 NFE exome

AF:

0.0194

Gnomad4 OTH exome

AF:

0.0260

GnomAD4 genome

AF:

0.0341

AC:

3780

AN:

110727

Hom.:

Cov.:

AF XY:

0.0298

AC XY:

984

AN XY:

33003

show subpopulations

Gnomad4 AFR

AF:

0.0717

Gnomad4 AMR

AF:

0.0165

Gnomad4 ASJ

AF:

0.0596

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0390

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.0202

Gnomad4 OTH

AF:

0.0348

Alfa

AF:

0.0331

Hom.:

250

Bravo

AF:

0.0368

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 04, 2013	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.96

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

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