rs5925760

Variant names:

• chrX-23365327-G-A
• rs5925760
• NM_173495.3:c.352-14264G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173495.3(PTCHD1):​c.352-14264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 111,144 control chromosomes in the GnomAD database, including 967 homozygotes. There are 4,589 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 0.13 (967 hom., 4589 hem., cov: 22)
• Consequence: PTCHD1 NM_173495.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173495.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCHD1	NM_173495.3	MANE Select	c.352-14264G>A		intron	N/A	NP_775766.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCHD1	ENST00000379361.5	TSL:1 MANE Select	c.352-14264G>A		intron	N/A	ENSP00000368666.4
	PTCHD1	ENST00000456522.1	TSL:1	c.157-27204G>A		intron	N/A	ENSP00000406663.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 14964 AN: 111090 Hom.: 966 Cov.: 22

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.0161

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.135 AC: 14964 AN: 111144 Hom.: 967 Cov.: 22 AF XY: 0.138 AC XY: 4589 AN XY: 33332

African (AFR) AF: 0.0334 AC: 1027 AN: 30703

American (AMR) AF: 0.196 AC: 2051 AN: 10455

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 189 AN: 2644

East Asian (EAS) AF: 0.154 AC: 543 AN: 3518

South Asian (SAS) AF: 0.245 AC: 637 AN: 2601

European-Finnish (FIN) AF: 0.260 AC: 1502 AN: 5786

Middle Eastern (MID) AF: 0.157 AC: 34 AN: 216

European-Non Finnish (NFE) AF: 0.165 AC: 8739 AN: 53027

Other (OTH) AF: 0.153 AC: 231 AN: 1511

Alfa AF: 0.135 Hom.: 3454

Bravo AF: 0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.4
DANN	Benign	0.85
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5925760; hg19: chrX-23383444;