X-23335211-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_173495.3(PTCHD1):c.336C>T(p.Thr112Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,207,697 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 117 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 0.00027 ( 0 hom., 12 hem., cov: 24)

Exomes 𝑓: 0.00033 ( 0 hom. 105 hem. )

Consequence

PTCHD1
NM_173495.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.785

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autism, susceptibility to, X-linked 4
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

PTCHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.011).

BP6

Variant X-23335211-C-T is Benign according to our data. Variant chrX-23335211-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 211970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.785 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD1	NM_173495.3 link	c.336C>T	p.Thr112Thr	synonymous_variant	Exon 1 of 3	ENST00000379361.5	NP_775766.2
PTCHD1	XM_011545449.4 link	c.336C>T	p.Thr112Thr	synonymous_variant	Exon 2 of 4		XP_011543751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5 link	c.336C>T	p.Thr112Thr	synonymous_variant	Exon 1 of 3	1	NM_173495.3	ENSP00000368666.4
PTCHD1	ENST00000456522.1 link	c.141C>T	p.Thr47Thr	synonymous_variant	Exon 1 of 2	1		ENSP00000406663.1

Frequencies

GnomAD3 genomes

AF:

0.000274

AC:

AN:

113077

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000963

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000921

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000507

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000238

AC:

AN:

181040

AF XY:

0.000195

show subpopulations

Gnomad AFR exome

AF:

0.0000765

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000513

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000327

AC:

358

AN:

1094620

Hom.:

Cov.:

AF XY:

0.000292

AC XY:

105

AN XY:

360120

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26322

American (AMR)

AF:

0.0000568

AC:

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19360

East Asian (EAS)

AF:

0.00

AC:

AN:

30188

South Asian (SAS)

AF:

0.00

AC:

AN:

54037

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40445

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.000415

AC:

348

AN:

838958

Other (OTH)

AF:

0.000130

AC:

AN:

45978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000274

AC:

AN:

113077

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

AN XY:

35223

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

31158

American (AMR)

AF:

0.0000921

AC:

AN:

10858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2787

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6347

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000507

AC:

AN:

53296

Other (OTH)

AF:

0.00

AC:

AN:

1519

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.000238

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000595

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PTCHD1: BP4, BP7, BS2 -

Jul 01, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 26, 2016

Genetic Services Laboratory, University of Chicago

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

-0.51

CADD

Benign

5.4

(source)

DANN

Benign

0.71

PhyloP100

-0.79

PromoterAI

-0.10

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over