rs5971108

Variant names:

• chrX-23364549-G-C
• rs5971108
• NM_173495.3:c.352-15042G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-23364549-G-C
• chrX-23364549-G-T

Variant summary

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

The NM_173495.3(PTCHD1):​c.352-15042G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 109,989 control chromosomes in the GnomAD database, including 3,622 homozygotes. There are 9,429 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 0.29 (3622 hom., 9429 hem., cov: 22)
• Consequence: PTCHD1 NM_173495.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173495.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCHD1	NM_173495.3	MANE Select	c.352-15042G>C		intron	N/A	NP_775766.2	Q96NR3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCHD1	ENST00000379361.5	TSL:1 MANE Select	c.352-15042G>C		intron	N/A	ENSP00000368666.4	Q96NR3-1
	PTCHD1	ENST00000456522.1	TSL:1	c.157-27982G>C		intron	N/A	ENSP00000406663.1	H7C2M0
	PTCHD1	ENST00000903588.1		c.352-15042G>C		intron	N/A	ENSP00000573647.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 31817 AN: 109940 Hom.: 3624 Cov.: 22

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.355

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.289 AC: 31827 AN: 109989 Hom.: 3622 Cov.: 22 AF XY: 0.292 AC XY: 9429 AN XY: 32305

African (AFR) AF: 0.237 AC: 7180 AN: 30294

American (AMR) AF: 0.404 AC: 4191 AN: 10371

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 402 AN: 2633

East Asian (EAS) AF: 0.574 AC: 1923 AN: 3353

South Asian (SAS) AF: 0.440 AC: 1142 AN: 2597

European-Finnish (FIN) AF: 0.339 AC: 1908 AN: 5633

Middle Eastern (MID) AF: 0.343 AC: 71 AN: 207

European-Non Finnish (NFE) AF: 0.273 AC: 14393 AN: 52721

Other (OTH) AF: 0.326 AC: 492 AN: 1510

Alfa AF: 0.137 Hom.: 657

Bravo AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.52
PhyloP100		0.91
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5971108;

hg19: chrX-23382666;