chrX-23394819-T-C

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

2

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

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
PTCHD1NM_173495.3 linkc.*634T>C 3_prime_UTR_variant Exon 3 of 3 ENST00000379361.5 NP_775766.2 Q96NR3-1X5DNX9
PTCHD1XM_011545449.4 linkc.*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
PTCHD1ENST00000379361.5 linkc.*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.:
24
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.:
34
Cov.:
0
AF XY:
0.397
AC XY:
56
AN XY:
141
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AF:
0.217
AC:
5
AN:
23
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AF:
0.500
AC:
4
AN:
8
European-Finnish (FIN)
AF:
0.468
AC:
131
AN:
280
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.418
AC:
69
AN:
165
Other (OTH)
AF:
0.333
AC:
3
AN:
9
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<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.:
24
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
0
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
0
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
DANN
Benign
0.56
PhyloP100
-0.041
Mutation Taster
=99/1
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

Publications

Other links and lift over

dbSNP: rs1317583; hg19: chrX-23412936; API