6-47878997-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384253.1(PTCHD4):​c.1838G>A​(p.Arg613Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,613,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

PTCHD4
NM_001384253.1 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75
Variant links:
Genes affected
PTCHD4 (HGNC:21345): (patched domain containing 4) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07142764).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTCHD4NM_001384253.1 linkuse as main transcriptc.1838G>A p.Arg613Lys missense_variant 5/5 ENST00000339488.9 NP_001371182.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTCHD4ENST00000339488.9 linkuse as main transcriptc.1838G>A p.Arg613Lys missense_variant 5/52 NM_001384253.1 ENSP00000341914 P1Q6ZW05-3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000280
AC:
7
AN:
249942
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135092
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000621
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461080
Hom.:
0
Cov.:
32
AF XY:
0.0000399
AC XY:
29
AN XY:
726858
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000468
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 15, 2024The c.1847G>A (p.R616K) alteration is located in exon 3 (coding exon 3) of the PTCHD4 gene. This alteration results from a G to A substitution at nucleotide position 1847, causing the arginine (R) at amino acid position 616 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.76
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
0.67
D
PrimateAI
Benign
0.46
T
PROVEAN
Benign
0.80
N
REVEL
Benign
0.22
Sift
Benign
0.25
T
Sift4G
Uncertain
0.010
D
Polyphen
0.0020
B
Vest4
0.11
MutPred
0.52
Loss of sheet (P = 0.0457);
MVP
0.57
MPC
0.099
ClinPred
0.15
T
GERP RS
4.1
Varity_R
0.096
gMVP
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763733920; hg19: chr6-47846733; API