Genetic Variant PRRT2:p.Ala3Asp (chr16-29813062-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145239.3(PRRT2):c.8C>A(p.Ala3Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PRRT2
NM_145239.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.95

Publications

0 publications found

Variant links:

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]

PRRT2 links:

ENSG00000280893 (HGNC:):

ENSG00000280893 links:

MVP-DT (HGNC:56029): (MVP divergent transcript)

MVP-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1612573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRT2	NM_145239.3 link	c.8C>A	p.Ala3Asp	missense_variant	Exon 2 of 4	ENST00000358758.12	NP_660282.2	Q7Z6L0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRT2	ENST00000358758.12 link	c.8C>A	p.Ala3Asp	missense_variant	Exon 2 of 4	1	NM_145239.3	ENSP00000351608.7		Q7Z6L0-1
ENSG00000280893	ENST00000609618.2 link	n.8C>A		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000476774.2		A0A0G2JLL6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445950

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32672

American (AMR)

AF:

0.00

AC:

AN:

41404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24856

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.00

AC:

AN:

84400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52906

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104910

Other (OTH)

AF:

0.0000168

AC:

AN:

59566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

.;.;T;.;T;.;.;.;.;T;.;T;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.73

T;T;.;.;T;T;T;T;T;.;T;.;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.5

.;.;L;L;.;L;.;.;L;L;.;L;L;.

PhyloP100

4.0

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.8

.;D;N;.;.;N;.;.;N;.;.;.;.;.

REVEL

Benign

0.13

Sift

Pathogenic

0.0

.;D;D;.;.;D;.;.;D;.;.;.;.;.

Sift4G

Uncertain

0.025

.;D;D;.;.;D;.;.;D;.;.;D;.;.

Polyphen

0.39, 0.74, 0.53

.;.;B;P;.;P;.;.;P;B;.;B;B;.

Vest4

0.47, 0.48, 0.39

MutPred

0.13

Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);

MVP

0.78

MPC

1.0

ClinPred

0.99

GERP RS

3.3

Varity_R

0.39

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over