Variant 6-32151815-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030651.4(PRRT1):c.13A>G(p.Lys5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,609,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

PRRT1
NM_030651.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRT1	NM_030651.4 linkuse as main transcript	c.13A>G	p.Lys5Glu	missense_variant	1/4	ENST00000211413.10	NP_085154.3	Q99946-1A0A1U9X8D6
PRRT1	NM_001363780.2 linkuse as main transcript	c.93A>G	p.Lys31Lys	synonymous_variant	3/6		NP_001350709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRT1	ENST00000211413.10 linkuse as main transcript	c.13A>G	p.Lys5Glu	missense_variant	1/4	1	NM_030651.4	ENSP00000211413.5		Q99946-1
ENSG00000285085	ENST00000428778.5 linkuse as main transcript	c.13A>G	p.Lys5Glu	missense_variant	4/5	3		ENSP00000396077.2		A2ABC7

Frequencies

GnomAD3 genomes

AF:

0.0000201

AC:

AN:

149578

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:

0.0000297

Gnomad OTH

AF:

0.000486

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1459630

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000201

AC:

AN:

149578

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72922

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000297

Gnomad4 OTH

AF:

0.000486

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Jan 10, 2022

The c.13A>G (p.K5E) alteration is located in exon 1 (coding exon 1) of the PRRT1 gene. This alteration results from a A to G substitution at nucleotide position 13, causing the lysine (K) at amino acid position 5 to be replaced by a glutamic acid (E). 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

0.30

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0098

Eigen

Benign

0.073

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.45

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Benign

0.21

Polyphen

0.88

Vest4

0.53

MutPred

0.18

Loss of ubiquitination at E5 (P = 0.0022);

MVP

0.69

ClinPred

0.59

GERP RS

4.0

Varity_R

0.17

gMVP

0.20

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