rs369975097

Positions:

• chrX-23335211-C-A
• chrX-23335211-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_173495.3(PTCHD1):​c.336C>A​(p.Thr112Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 1,207,697 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.0000088 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.0000064 (0 hom. 2 hem.)
• Consequence: PTCHD1 NM_173495.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.785 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD1	NM_173495.3	c.336C>A	p.Thr112Thr	synonymous_variant	1/3	ENST00000379361.5	NP_775766.2
PTCHD1	XM_011545449.4	c.336C>A	p.Thr112Thr	synonymous_variant	2/4		XP_011543751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5	c.336C>A	p.Thr112Thr	synonymous_variant	1/3	1	NM_173495.3	ENSP00000368666.4
PTCHD1	ENST00000456522.1	c.141C>A	p.Thr47Thr	synonymous_variant	1/2	1		ENSP00000406663.1

Frequencies

GnomAD3 genomes AF: 0.00000884 AC: 1 AN: 113077 Hom.: 0 Cov.: 24 AF XY: 0.0000284 AC XY: 1 AN XY: 35223

Gnomad AFR AF: 0.0000321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000639 AC: 7 AN: 1094620 Hom.: 0 Cov.: 29 AF XY: 0.00000555 AC XY: 2 AN XY: 360120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000834

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000884 AC: 1 AN: 113077 Hom.: 0 Cov.: 24 AF XY: 0.0000284 AC XY: 1 AN XY: 35223

Gnomad4 AFR AF: 0.0000321

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.7
DANN	Benign	0.61

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: rs369975097; hg19: chrX-23353328;