6-47878997-C-T
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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
NM_001384253.1 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 3.75
Genes affected
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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 |
---|---|---|---|---|---|---|---|---|
PTCHD4 | NM_001384253.1 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
PTCHD4 | ENST00000339488.9 | c.1838G>A | p.Arg613Lys | missense_variant | 5/5 | 2 | NM_001384253.1 | ENSP00000341914 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249942Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135092
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GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461080Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29AN XY: 726858
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74292
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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 submitter | clinical testing | Ambry Genetics | May 15, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of sheet (P = 0.0457);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at