Variant X-23334924-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_173495.3(PTCHD1):c.49C>G(p.Leu17Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000734 in 1,089,858 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000073 ( 0 hom. 2 hem. )

Consequence

PTCHD1
NM_173495.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.49

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD1	NM_173495.3 linkuse as main transcript	c.49C>G	p.Leu17Val	missense_variant	1/3	ENST00000379361.5	NP_775766.2
PTCHD1	XM_011545449.4 linkuse as main transcript	c.49C>G	p.Leu17Val	missense_variant	2/4		XP_011543751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5 linkuse as main transcript	c.49C>G	p.Leu17Val	missense_variant	1/3	1	NM_173495.3	ENSP00000368666	P1	Q96NR3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

160315

Hom.:

AF XY:

0.00

AC XY:

AN XY:

51767

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000288

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000734

AC:

AN:

1089858

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

357038

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000954

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.49C>G (p.L17V) alteration is located in exon 1 (coding exon 1) of the PTCHD1 gene. This alteration results from a C to G substitution at nucleotide position 49, causing the leucine (L) at amino acid position 17 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 26, 2023

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.91

MetaRNN

Uncertain

0.56

MetaSVM

Uncertain

-0.083

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.57

Sift

Uncertain

0.018

Sift4G

Pathogenic

0.0

Polyphen

0.40

Vest4

0.44

MutPred

0.66

Loss of helix (P = 0.0558);

MVP

0.98

MPC

1.5

ClinPred

0.54

GERP RS

4.3

Varity_R

0.48

gMVP

0.83

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