X-23394819-T-C

Position:

• chrX-23394819-T-C

Variant summary

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

The NM_173495.3(PTCHD1):​c.*634T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.60 (15356 hom., 19881 hem., cov: 24)
  • Exomes 𝑓: 0.44 (34 hom. 56 hem.)
  • Failed GnomAD Quality Control
• Consequence: PTCHD1 NM_173495.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.89).
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD1	NM_173495.3	c.*634T>C		3_prime_UTR_variant	3/3	ENST00000379361.5	NP_775766.2
PTCHD1	XM_011545449.4	c.*634T>C		3_prime_UTR_variant	4/4		XP_011543751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5	c.*634T>C		3_prime_UTR_variant	3/3	1	NM_173495.3	ENSP00000368666.4

Frequencies

GnomAD3 genomes AF: 0.599 AC: 66756 AN: 111379 Hom.: 15359 Cov.: 24 AF XY: 0.591 AC XY: 19823 AN XY: 33557

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.562

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.437 AC: 212 AN: 485 Hom.: 34 Cov.: 0 AF XY: 0.397 AC XY: 56 AN XY: 141

Gnomad4 AMR exome AF: 0.217

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.600 AC: 66807 AN: 111432 Hom.: 15356 Cov.: 24 AF XY: 0.591 AC XY: 19881 AN XY: 33620

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.594

Alfa AF: 0.518 Hom.: 12184

Bravo AF: 0.622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.56

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: rs1317583; hg19: chrX-23412936;