X-23334930-C-A

Position:

• chrX-23334930-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173495.3(PTCHD1):​c.55C>A​(p.His19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: PTCHD1 NM_173495.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.999

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD1	NM_173495.3	c.55C>A	p.His19Asn	missense_variant	1/3	ENST00000379361.5	NP_775766.2
PTCHD1	XM_011545449.4	c.55C>A	p.His19Asn	missense_variant	2/4		XP_011543751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5	c.55C>A	p.His19Asn	missense_variant	1/3	1	NM_173495.3	ENSP00000368666	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

PTCHD1: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.53	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.21
Sift	Benign	0.19	T
Sift4G	Benign	0.087	T
Polyphen		0.28	B
Vest4		0.27
MutPred		0.74		Loss of catalytic residue at H19 (P = 0.0803);
MVP		0.72
MPC		0.66
ClinPred		0.25	T
GERP RS		4.3
Varity_R		0.16
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-23353047;