Genetic Variant PTCHD1:c.*634T>C (chrX-23394819-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0410

Publications

2 publications found

Variant links:

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

PTCHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTCHD1	NM_173495.3 link	c.*634T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000379361.5	NP_775766.2	Q96NR3-1X5DNX9
PTCHD1	XM_011545449.4 link	c.*634T>C		3_prime_UTR_variant	Exon 4 of 4		XP_011543751.1	Q96NR3-1X5DNX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD1	ENST00000379361.5 link	c.*634T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_173495.3	ENSP00000368666.4		Q96NR3-1

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

66756

AN:

111379

Hom.:

15359

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.397

AC XY:

AN XY:

141

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.217

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.468

AC:

131

AN:

280

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.418

AC:

AN:

165

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.600

AC:

66807

AN:

111432

Hom.:

15356

Cov.:

AF XY:

0.591

AC XY:

19881

AN XY:

33620

show subpopulations

African (AFR)

AF:

0.872

AC:

26730

AN:

30667

American (AMR)

AF:

0.570

AC:

6023

AN:

10572

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

1527

AN:

2637

East Asian (EAS)

AF:

0.636

AC:

2227

AN:

3502

South Asian (SAS)

AF:

0.460

AC:

1226

AN:

2666

European-Finnish (FIN)

AF:

0.443

AC:

2651

AN:

5986

Middle Eastern (MID)

AF:

0.566

AC:

120

AN:

212

European-Non Finnish (NFE)

AF:

0.474

AC:

25135

AN:

52989

Other (OTH)

AF:

0.594

AC:

905

AN:

1524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

886

1772

2658

3544

4430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.527

Hom.:

14320

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

(source)

DANN

Benign

0.56

PhyloP100

-0.041

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over