rs144982584

Variant names:

• chrX-23379896-C-T
• rs144982584
• NM_173495.3:c.657C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_173495.3(PTCHD1):​c.657C>T​(p.Asn219Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,210,242 control chromosomes in the GnomAD database, including 3 homozygotes. There are 1,014 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., 47 hem., cov: 23)
  • Exomes 𝑓: 0.0027 (2 hom. 967 hem.)
• Consequence: PTCHD1 NM_173495.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.01
• Publications: 0 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant X-23379896-C-T is Benign according to our data. Variant chrX-23379896-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 195428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.01 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 47 XL gene

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.657C>T	p.Asn219Asn	synonymous	Exon 2 of 3	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.657C>T	p.Asn219Asn	synonymous	Exon 2 of 3	ENSP00000368666.4	Q96NR3-1
	PTCHD1	ENST00000456522.1	TSL:1	c.157-12635C>T		intron	N/A	ENSP00000406663.1	H7C2M0
	PTCHD1	ENST00000903588.1		c.657C>T	p.Asn219Asn	synonymous	Exon 3 of 4	ENSP00000573647.1

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 198 AN: 112196 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.000551

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000753

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000376

Gnomad FIN AF: 0.00229

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00132

GnomAD2 exomes AF: 0.00189 AC: 347 AN: 183471 AF XY: 0.00199

Gnomad AFR exome AF: 0.000608

Gnomad AMR exome AF: 0.000510

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00369

Gnomad NFE exome AF: 0.00309

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00270 AC: 2966 AN: 1097991 Hom.: 2 Cov.: 31 AF XY: 0.00266 AC XY: 967 AN XY: 363347

African (AFR) AF: 0.000265 AC: 7 AN: 26398

American (AMR) AF: 0.000625 AC: 22 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.000573 AC: 31 AN: 54143

European-Finnish (FIN) AF: 0.00375 AC: 152 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00312 AC: 2629 AN: 841898

Other (OTH) AF: 0.00271 AC: 125 AN: 46086

GnomAD4 genome AF: 0.00177 AC: 199 AN: 112251 Hom.: 1 Cov.: 23 AF XY: 0.00137 AC XY: 47 AN XY: 34411

African (AFR) AF: 0.000549 AC: 17 AN: 30945

American (AMR) AF: 0.000752 AC: 8 AN: 10643

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.000753 AC: 2 AN: 2655

European-Finnish (FIN) AF: 0.00229 AC: 14 AN: 6121

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00293 AC: 156 AN: 53215

Other (OTH) AF: 0.00130 AC: 2 AN: 1538

Alfa AF: 0.00135 Hom.: 9

Bravo AF: 0.00155

EpiCase AF: 0.00300

EpiControl AF: 0.00273

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		3.0
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

Other links and lift over

dbSNP: rs144982584; hg19: chrX-23398013;