dbSNP rs369975097: PTCHD1:p.Thr112Thr (chrX-23335211-C-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_173495.3(PTCHD1):c.336C>A(p.Thr112Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 1,207,697 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. Synonymous variant affecting the same amino acid position (i.e. T112T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000064 ( 0 hom. 2 hem. )

Consequence

PTCHD1
NM_173495.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.785

Publications

0 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.043).

BP7

Synonymous conserved (PhyloP=-0.785 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD1	NM_173495.3 link	c.336C>A	p.Thr112Thr	synonymous_variant	Exon 1 of 3	ENST00000379361.5	NP_775766.2	Q96NR3-1X5DNX9
PTCHD1	XM_011545449.4 link	c.336C>A	p.Thr112Thr	synonymous_variant	Exon 2 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.336C>A	p.Thr112Thr	synonymous_variant	Exon 1 of 3	1	NM_173495.3	ENSP00000368666.4		Q96NR3-1
PTCHD1	ENST00000456522.1 link	c.141C>A	p.Thr47Thr	synonymous_variant	Exon 1 of 2	1		ENSP00000406663.1		H7C2M0

Frequencies

GnomAD3 genomes

AF:

0.00000884

AC:

AN:

113077

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000639

AC:

AN:

1094620

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

360120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26322

American (AMR)

AF:

0.00

AC:

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19360

East Asian (EAS)

AF:

0.00

AC:

AN:

30188

South Asian (SAS)

AF:

0.00

AC:

AN:

54037

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40445

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00000834

AC:

AN:

838958

Other (OTH)

AF:

0.00

AC:

AN:

45978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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

AF:

0.00000884

AC:

AN:

113077

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

35223

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31158

American (AMR)

AF:

0.00

AC:

AN:

10858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2787

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6347

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53296

Other (OTH)

AF:

0.00

AC:

AN:

1519

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.7

(source)

DANN

Benign

0.61

PhyloP100

-0.79

PromoterAI

-0.066

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over