chrX-23335211-C-T

Variant names:

• chrX-23335211-C-T
• rs369975097
• NM_173495.3:c.336C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_173495.3(PTCHD1):​c.336C>T​(p.Thr112Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,207,697 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 117 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 0.00027 (0 hom., 12 hem., cov: 24)
  • Exomes 𝑓: 0.00033 (0 hom. 105 hem.)
• Consequence: PTCHD1 NM_173495.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.785
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.011).
• BP6: Variant X-23335211-C-T is Benign according to our data. Variant chrX-23335211-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 211970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.785 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 12 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.336C>T	p.Thr112Thr	synonymous	Exon 1 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.336C>T	p.Thr112Thr	synonymous	Exon 1 of 3	ENSP00000368666.4	Q96NR3-1
	PTCHD1	ENST00000456522.1	TSL:1	c.141C>T	p.Thr47Thr	synonymous	Exon 1 of 2	ENSP00000406663.1	H7C2M0
	PTCHD1	ENST00000903588.1		c.336C>T	p.Thr112Thr	synonymous	Exon 2 of 4	ENSP00000573647.1

Frequencies

GnomAD3 genomes AF: 0.000274 AC: 31 AN: 113077 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000963

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000921

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: 0.000507

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000238 AC: 43 AN: 181040 AF XY: 0.000195

Gnomad AFR exome AF: 0.0000765

Gnomad AMR exome AF: 0.0000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000513

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000327 AC: 358 AN: 1094620 Hom.: 0 Cov.: 29 AF XY: 0.000292 AC XY: 105 AN XY: 360120

African (AFR) AF: 0.0000380 AC: 1 AN: 26322

American (AMR) AF: 0.0000568 AC: 2 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19360

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.00 AC: 0 AN: 54037

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40445

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.000415 AC: 348 AN: 838958

Other (OTH) AF: 0.000130 AC: 6 AN: 45978

GnomAD4 genome AF: 0.000274 AC: 31 AN: 113077 Hom.: 0 Cov.: 24 AF XY: 0.000341 AC XY: 12 AN XY: 35223

African (AFR) AF: 0.0000963 AC: 3 AN: 31158

American (AMR) AF: 0.0000921 AC: 1 AN: 10858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3541

South Asian (SAS) AF: 0.00 AC: 0 AN: 2787

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6347

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000507 AC: 27 AN: 53296

Other (OTH) AF: 0.00 AC: 0 AN: 1519

Alfa AF: 0.000145 Hom.: 1

Bravo AF: 0.000238

EpiCase AF: 0.000273

EpiControl AF: 0.0000595

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.4
DANN	Benign	0.71
PhyloP100		-0.79
PromoterAI		-0.10	Neutral
Mutation Taster		=99/1	polymorphism

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: rs369975097; hg19: chrX-23353328;