X-23356765-T-G

Variant names:

• chrX-23356765-T-G
• rs7052177
• NM_173495.3:c.351+21539T>G

Variant summary

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

The ENST00000379361.5(PTCHD1):​c.351+21539T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 111,325 control chromosomes in the GnomAD database, including 3,250 homozygotes. There are 6,778 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 0.22 (3250 hom., 6778 hem., cov: 23)
• Consequence: PTCHD1 ENST00000379361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379361.5. 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.351+21539T>G		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.351+21539T>G		intron	N/A	ENSP00000368666.4
	PTCHD1	ENST00000456522.1	TSL:1	c.156+21539T>G		intron	N/A	ENSP00000406663.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 24094 AN: 111271 Hom.: 3246 Cov.: 23

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.0938

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.157

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.217 AC: 24133 AN: 111325 Hom.: 3250 Cov.: 23 AF XY: 0.202 AC XY: 6778 AN XY: 33561

African (AFR) AF: 0.502 AC: 15290 AN: 30430

American (AMR) AF: 0.105 AC: 1110 AN: 10533

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 365 AN: 2643

East Asian (EAS) AF: 0.0265 AC: 95 AN: 3579

South Asian (SAS) AF: 0.135 AC: 354 AN: 2613

European-Finnish (FIN) AF: 0.121 AC: 732 AN: 6042

Middle Eastern (MID) AF: 0.148 AC: 32 AN: 216

European-Non Finnish (NFE) AF: 0.109 AC: 5790 AN: 53067

Other (OTH) AF: 0.198 AC: 301 AN: 1520

Alfa AF: 0.153 Hom.: 8984

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.54
PhyloP100		0.35
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: rs7052177; hg19: chrX-23374882;