dbSNP rs763634807: PRRT2:p.Ala139Thr (chr16-29813469-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145239.3(PRRT2):c.415G>A(p.Ala139Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A139A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

PRRT2
NM_145239.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.435

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046206474).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145239.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRRT2	NM_145239.3	MANE Select	c.415G>A	p.Ala139Thr	missense	Exon 2 of 4	NP_660282.2	Q7Z6L0-1
PRRT2	NM_001256442.2		c.415G>A	p.Ala139Thr	missense	Exon 2 of 3	NP_001243371.1	Q7Z6L0-2
PRRT2	NM_001438121.1		c.415G>A	p.Ala139Thr	missense	Exon 2 of 3	NP_001425050.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.415G>A	p.Ala139Thr	missense	Exon 2 of 4	ENSP00000351608.7	Q7Z6L0-1
ENSG00000280893	ENST00000609618.2	TSL:5	n.415G>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2	A0A0G2JLL6
PRRT2	ENST00000567659.3	TSL:2	c.415G>A	p.Ala139Thr	missense	Exon 2 of 3	ENSP00000456226.1	Q7Z6L0-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152108

Hom.:

Cov.:

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250602

AF XY:

0.00000738

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000780

AC:

114

AN:

1461552

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000103

AC:

114

AN:

1111844

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000282

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Episodic kinesigenic dyskinesia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.8

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.61

M_CAP

Benign

0.0062

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.43

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.26

REVEL

Benign

0.024

Sift

Uncertain

0.0060

Sift4G

Benign

0.17

Polyphen

0.0010

Vest4

0.13

MutPred

0.23

Gain of phosphorylation at A139 (P = 4e-04)

MVP

0.67

MPC

0.24

ClinPred

0.024

GERP RS

1.1

Varity_R

0.055

gMVP

0.071

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over