Variant rs144982584 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_173495.3(PTCHD1):c.657C>T(p.Asn219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,210,242 control chromosomes in the GnomAD database, including 3 homozygotes. There are 1,014 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., 47 hem., cov: 23)

Exomes 𝑓: 0.0027 ( 2 hom. 967 hem. )

Consequence

PTCHD1
NM_173495.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.01

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 -15 ACMG points.

BP4

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

BP6

Variant X-23379896-C-T is Benign according to our data. Variant chrX-23379896-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 195428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.01 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 47 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD1	NM_173495.3 linkuse as main transcript	c.657C>T	p.Asn219=	synonymous_variant	2/3	ENST00000379361.5	NP_775766.2
PTCHD1	XM_011545449.4 linkuse as main transcript	c.657C>T	p.Asn219=	synonymous_variant	3/4		XP_011543751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5 linkuse as main transcript	c.657C>T	p.Asn219=	synonymous_variant	2/3	1	NM_173495.3	ENSP00000368666	P1	Q96NR3-1
PTCHD1	ENST00000456522.1 linkuse as main transcript	c.159-12635C>T		intron_variant		1		ENSP00000406663

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

198

AN:

112196

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

34346

show subpopulations

Gnomad AFR

AF:

0.000551

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000753

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000376

Gnomad FIN

AF:

0.00229

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00293

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.00189

AC:

347

AN:

183471

Hom.:

AF XY:

0.00199

AC XY:

135

AN XY:

67901

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.000510

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000367

Gnomad FIN exome

AF:

0.00369

Gnomad NFE exome

AF:

0.00309

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00270

AC:

2966

AN:

1097991

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

967

AN XY:

363347

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.000625

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000573

Gnomad4 FIN exome

AF:

0.00375

Gnomad4 NFE exome

AF:

0.00312

Gnomad4 OTH exome

AF:

0.00271

GnomAD4 genome

AF:

0.00177

AC:

199

AN:

112251

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

34411

show subpopulations

Gnomad4 AFR

AF:

0.000549

Gnomad4 AMR

AF:

0.000752

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000753

Gnomad4 FIN

AF:

0.00229

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.00130

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.00155

EpiCase

AF:

0.00300

EpiControl

AF:

0.00273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 02, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 12, 2014	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2017

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.61

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