X-23356765-T-G

Variant names:

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

Variant summary

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

The NM_173495.3(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 NM_173495.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD1	NM_173495.3	c.351+21539T>G		intron_variant	Intron 1 of 2	ENST00000379361.5	NP_775766.2
PTCHD1	XM_011545449.4	c.351+21539T>G		intron_variant	Intron 2 of 3		XP_011543751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5	c.351+21539T>G		intron_variant	Intron 1 of 2	1	NM_173495.3	ENSP00000368666.4
PTCHD1	ENST00000456522.1	c.156+21539T>G		intron_variant	Intron 1 of 1	1		ENSP00000406663.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 24094 AN: 111271 Hom.: 3246 Cov.: 23 AF XY: 0.201 AC XY: 6747 AN XY: 33497

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

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0265

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.198

Alfa AF: 0.126 Hom.: 4557

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.54

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: rs7052177; hg19: chrX-23374882;