ENST00000642324.1:c.1418A>G

Variant summary

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

The ENST00000642324.1(PTCHD3):​c.1418A>G​(p.Asp473Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,603,836 control chromosomes in the GnomAD database, including 352,143 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 29328 hom., cov: 25)
Exomes 𝑓: 0.66 ( 322815 hom. )

Consequence

PTCHD3
ENST00000642324.1 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

29 publications found
Variant links:
Genes affected
PTCHD3 (HGNC:24776): (patched domain containing 3 (gene/pseudogene)) Predicted to be located in sperm midpiece. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (MetaRNN=4.6696587E-6).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTCHD3NM_001034842.5 linkc.1418A>G p.Asp473Gly missense_variant Exon 4 of 4 NP_001030014.2 Q3KNS1A0A8Q3VUI5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTCHD3ENST00000642324.1 linkc.1418A>G p.Asp473Gly missense_variant Exon 4 of 4 ENSP00000495205.1

Frequencies

GnomAD3 genomes
AF:
0.621
AC:
92951
AN:
149754
Hom.:
29303
Cov.:
25
show subpopulations
Gnomad AFR
AF:
0.546
Gnomad AMI
AF:
0.745
Gnomad AMR
AF:
0.562
Gnomad ASJ
AF:
0.748
Gnomad EAS
AF:
0.342
Gnomad SAS
AF:
0.663
Gnomad FIN
AF:
0.685
Gnomad MID
AF:
0.705
Gnomad NFE
AF:
0.678
Gnomad OTH
AF:
0.641
GnomAD2 exomes
AF:
0.613
AC:
150155
AN:
244942
AF XY:
0.630
show subpopulations
Gnomad AFR exome
AF:
0.545
Gnomad AMR exome
AF:
0.429
Gnomad ASJ exome
AF:
0.748
Gnomad EAS exome
AF:
0.350
Gnomad FIN exome
AF:
0.675
Gnomad NFE exome
AF:
0.677
Gnomad OTH exome
AF:
0.638
GnomAD4 exome
AF:
0.659
AC:
958583
AN:
1453974
Hom.:
322815
Cov.:
43
AF XY:
0.663
AC XY:
479703
AN XY:
723742
show subpopulations
African (AFR)
AF:
0.545
AC:
18224
AN:
33446
American (AMR)
AF:
0.447
AC:
20001
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.747
AC:
19507
AN:
26114
East Asian (EAS)
AF:
0.275
AC:
10908
AN:
39690
South Asian (SAS)
AF:
0.697
AC:
60053
AN:
86196
European-Finnish (FIN)
AF:
0.680
AC:
32429
AN:
47668
Middle Eastern (MID)
AF:
0.739
AC:
4259
AN:
5766
European-Non Finnish (NFE)
AF:
0.679
AC:
753483
AN:
1110074
Other (OTH)
AF:
0.659
AC:
39719
AN:
60302
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
Heterozygous variant carriers
0
16198
32396
48595
64793
80991
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
19170
38340
57510
76680
95850
<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:
0.621
AC:
93024
AN:
149862
Hom.:
29328
Cov.:
25
AF XY:
0.622
AC XY:
45473
AN XY:
73056
show subpopulations
African (AFR)
AF:
0.547
AC:
22287
AN:
40746
American (AMR)
AF:
0.561
AC:
8426
AN:
15014
Ashkenazi Jewish (ASJ)
AF:
0.748
AC:
2582
AN:
3450
East Asian (EAS)
AF:
0.343
AC:
1748
AN:
5102
South Asian (SAS)
AF:
0.663
AC:
3126
AN:
4714
European-Finnish (FIN)
AF:
0.685
AC:
6902
AN:
10082
Middle Eastern (MID)
AF:
0.707
AC:
205
AN:
290
European-Non Finnish (NFE)
AF:
0.678
AC:
45744
AN:
67474
Other (OTH)
AF:
0.637
AC:
1326
AN:
2080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
1509
3018
4527
6036
7545
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
766
1532
2298
3064
3830
<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:
0.653
Hom.:
107106
Bravo
AF:
0.602
TwinsUK
AF:
0.682
AC:
2529
ALSPAC
AF:
0.680
AC:
2620
ESP6500AA
AF:
0.534
AC:
2355
ESP6500EA
AF:
0.681
AC:
5856
ExAC
AF:
0.618
AC:
75049
Asia WGS
AF:
0.505
AC:
1759
AN:
3478
EpiCase
AF:
0.691
EpiControl
AF:
0.695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
14
DANN
Benign
0.24
DEOGEN2
Benign
0.25
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.071
N
MetaRNN
Benign
0.0000047
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.3
L;.
PhyloP100
2.1
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-2.9
D;.
REVEL
Benign
0.17
Sift
Benign
0.41
T;.
Sift4G
Benign
0.22
T;T
Polyphen
0.0010
B;.
Vest4
0.15
MPC
0.13
ClinPred
0.014
T
GERP RS
-0.12
Varity_R
0.11
Mutation Taster
=97/3
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: rs2429485; hg19: chr10-27688109; COSMIC: COSV71256303; API