Variant 6-32150501-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030651.4(PRRT1):c.425A>C(p.Gln142Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,439,844 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

PRRT1
NM_030651.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

PRRT1 (HGNC:13943): (proline rich transmembrane protein 1) Enables identical protein binding activity. Predicted to be involved in several processes, including long-term synaptic depression; protein localization to cell surface; and regulation of AMPA receptor activity. Predicted to act upstream of or within several processes, including learning or memory; long-term synaptic potentiation; and synapse organization. Predicted to be located in postsynaptic density membrane and synaptic vesicle membrane. Predicted to be active in glutamatergic synapse and membrane. Predicted to be integral component of postsynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

PRRT1 links:

ENSG00000285085 (HGNC:):

ENSG00000285085 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028747708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRT1	NM_030651.4 linkuse as main transcript	c.425A>C	p.Gln142Pro	missense_variant	2/4	ENST00000211413.10	NP_085154.3	Q99946-1A0A1U9X8D6
PRRT1	NM_001363780.2 linkuse as main transcript	c.182A>C	p.Gln61Pro	missense_variant	4/6		NP_001350709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRT1	ENST00000211413.10 linkuse as main transcript	c.425A>C	p.Gln142Pro	missense_variant	2/4	1	NM_030651.4	ENSP00000211413.5		Q99946-1
ENSG00000285085	ENST00000428778.5 linkuse as main transcript	c.102A>C	p.Pro34Pro	synonymous_variant	5/5	3		ENSP00000396077.2		A2ABC7

Frequencies

GnomAD3 genomes

AF:

0.000822

AC:

125

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000868

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000839

AC:

AN:

76278

Hom.:

AF XY:

0.000781

AC XY:

AN XY:

44832

show subpopulations

Gnomad AFR exome

AF:

0.000557

Gnomad AMR exome

AF:

0.00146

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:

0.00136

Gnomad OTH exome

AF:

0.000735

GnomAD4 exome

AF:

0.00101

AC:

1302

AN:

1287664

Hom.:

Cov.:

AF XY:

0.000952

AC XY:

601

AN XY:

631368

show subpopulations

Gnomad4 AFR exome

AF:

0.000518

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000431

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152180

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000868

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000763

Hom.:

Bravo

AF:

0.00114

ExAC

AF:

0.000648

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 17, 2024

The c.425A>C (p.Q142P) alteration is located in exon 2 (coding exon 2) of the PRRT1 gene. This alteration results from a A to C substitution at nucleotide position 425, causing the glutamine (Q) at amino acid position 142 to be replaced by a proline (P). 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

0.059

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0081

T;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.63

T;T;.

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-0.34

N;.;.

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.090

N;N;D

REVEL

Uncertain

0.43

Sift

Benign

0.24

T;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.29

MVP

0.41

ClinPred

0.015

GERP RS

2.1

Varity_R

0.21

gMVP

0.34

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over