rs5971108

Positions:

• chrX-23364549-G-C
• chrX-23364549-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173495.3(PTCHD1):​c.352-15042G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 109,989 control chromosomes in the GnomAD database, including 3,622 homozygotes. There are 9,429 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (3622 hom., 9429 hem., cov: 22)
• Consequence: PTCHD1 NM_173495.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD1	NM_173495.3	c.352-15042G>C		intron_variant		ENST00000379361.5
PTCHD1	XM_011545449.4	c.352-15042G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCHD1	ENST00000379361.5	c.352-15042G>C		intron_variant		1	NM_173495.3	P1
PTCHD1	ENST00000456522.1	c.159-27982G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 31817 AN: 109940 Hom.: 3624 Cov.: 22 AF XY: 0.292 AC XY: 9406 AN XY: 32246

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.355

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 31827 AN: 109989 Hom.: 3622 Cov.: 22 AF XY: 0.292 AC XY: 9429 AN XY: 32305

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.326

Alfa AF: 0.137 Hom.: 657

Bravo AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs5971108; hg19: chrX-23382666;