rs138702144

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_173495.3(PTCHD1):c.1332C>T(p.Val444Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,210,524 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 45 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., 20 hem., cov: 23)

Exomes 𝑓: 0.000077 ( 0 hom. 25 hem. )

Consequence

PTCHD1
NM_173495.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.929

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant X-23392850-C-T is Benign according to our data. Variant chrX-23392850-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211966.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=0.929 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD1	NM_173495.3 link	c.1332C>T	p.Val444Val	synonymous_variant	Exon 3 of 3	ENST00000379361.5	NP_775766.2	Q96NR3-1X5DNX9
PTCHD1	XM_011545449.4 link	c.1332C>T	p.Val444Val	synonymous_variant	Exon 4 of 4		XP_011543751.1	Q96NR3-1X5DNX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5 link	c.1332C>T	p.Val444Val	synonymous_variant	Exon 3 of 3	1	NM_173495.3	ENSP00000368666.4		Q96NR3-1
PTCHD1	ENST00000456522.1 link	c.*167C>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000406663.1		H7C2M0

Frequencies

GnomAD3 genomes

AF:

0.000613

AC:

AN:

112569

Hom.:

Cov.:

AF XY:

0.000576

AC XY:

AN XY:

34729

show subpopulations

Gnomad AFR

AF:

0.00213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000939

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000169

AC:

AN:

182977

Hom.:

AF XY:

0.0000888

AC XY:

AN XY:

67549

show subpopulations

Gnomad AFR exome

AF:

0.00190

Gnomad AMR exome

AF:

0.000182

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000765

AC:

AN:

1097904

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

363258

show subpopulations

Gnomad4 AFR exome

AF:

0.00223

Gnomad4 AMR exome

AF:

0.000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000475

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000613

AC:

AN:

112620

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

AN XY:

34790

show subpopulations

Gnomad4 AFR

AF:

0.00213

Gnomad4 AMR

AF:

0.0000938

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000371

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000695

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 28, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Uncertain:1

Apr 22, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jul 11, 2016

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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

-0.43

CADD

Benign

7.8

DANN

Benign

0.69

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