rs148630483

chrX-23380037-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_173495.3(PTCHD1):c.798C>T(p.Arg266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,209,791 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000028 (0 hom. 15 hem.)
• Consequence: PTCHD1 NM_173495.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.128

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-0.128 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD1	NM_173495.3	c.798C>T	p.Arg266=	synonymous_variant	2/3	ENST00000379361.5
PTCHD1	XM_011545449.4	c.798C>T	p.Arg266=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCHD1	ENST00000379361.5	c.798C>T	p.Arg266=	synonymous_variant	2/3	1	NM_173495.3	P1
PTCHD1	ENST00000456522.1	c.159-12494C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0000535 AC: 6 AN: 112079 Hom.: 0 Cov.: 22 AF XY: 0.0000292 AC XY: 1 AN XY: 34231

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000282

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000872 AC: 16 AN: 183513 Hom.: 0 AF XY: 0.000103 AC XY: 7 AN XY: 67941

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.000441

GnomAD4 exome AF: 0.0000282 AC: 31 AN: 1097712 Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 15 AN XY: 363068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000369

Gnomad4 ASJ exome AF: 0.0000516

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000178

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome AF: 0.0000535 AC: 6 AN: 112079 Hom.: 0 Cov.: 22 AF XY: 0.0000292 AC XY: 1 AN XY: 34231

Gnomad4 AFR AF: 0.0000325

Gnomad4 AMR AF: 0.000282

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000376

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000831

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 29, 2014

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	0.56
Dann	Benign	0.55

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: rs148630483; hg19: chrX-23398154;