chr16-29813066-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_145239.3(PRRT2):c.12C>A(p.Ser4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,448,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
PRRT2
NM_145239.3 missense
NM_145239.3 missense
Scores
3
10
Clinical Significance
Conservation
PhyloP100: 0.0890
Genes affected
PRRT2 (HGNC:30500): (proline rich transmembrane protein 2) This gene encodes a transmembrane protein containing a proline-rich domain in its N-terminal half. Studies in mice suggest that it is predominantly expressed in brain and spinal cord in embryonic and postnatal stages. Mutations in this gene are associated with episodic kinesigenic dyskinesia-1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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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=0.13736045).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRRT2 | NM_145239.3 | c.12C>A | p.Ser4Arg | missense_variant | 2/4 | ENST00000358758.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.12C>A | p.Ser4Arg | missense_variant | 2/4 | 1 | NM_145239.3 | P1 | |
MVP-DT | ENST00000569039.5 | n.246-2893G>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000418 AC: 1AN: 239396Hom.: 0 AF XY: 0.00000771 AC XY: 1AN XY: 129752
GnomAD3 exomes
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129752
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GnomAD4 exome AF: 0.00000345 AC: 5AN: 1448428Hom.: 0 Cov.: 32 AF XY: 0.00000555 AC XY: 4AN XY: 720076
GnomAD4 exome
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1448428
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32
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4
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720076
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Episodic kinesigenic dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PRRT2-related conditions. This variant is present in population databases (rs757148846, ExAC 0.002%). This sequence change replaces serine with arginine at codon 4 of the PRRT2 protein (p.Ser4Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;.;.;T;T;T;T;T;.;T;.;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
Polyphen
0.39, 0.74, 0.53
.;.;B;P;.;P;.;.;P;B;.;B;B;.
Vest4
0.36, 0.35, 0.32
MutPred
Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);Loss of phosphorylation at S4 (P = 0.0018);
MVP
0.82
MPC
0.87
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at