Genetic Variant PRR3:p.Pro38Leu (chr6-30558156-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_025263.4(PRR3):c.113C>T(p.Pro38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,612,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

PRR3
NM_025263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Variant links:

Genes affected

PRR3 (HGNC:21149): (proline rich 3) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PRR3 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
PRR3	NM_025263.4 link	c.113C>T	p.Pro38Leu	missense_variant	Exon 2 of 4	ENST00000376560.8	NP_079539.2	P79522-1Q96QB9
PRR3	XM_047419381.1 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 2 of 3		XP_047275337.1
PRR3	NM_001077497.3 link	c.106+706C>T		intron_variant	Intron 1 of 2		NP_001070965.1	B3KQA4
PRR3	XM_047419382.1 link	c.264+706C>T		intron_variant	Intron 1 of 1		XP_047275338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR3	ENST00000376560.8 link	c.113C>T	p.Pro38Leu	missense_variant	Exon 2 of 4	1	NM_025263.4	ENSP00000365744.4		P79522-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

244676

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

133912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000236

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000373

AC:

545

AN:

1460612

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

282

AN XY:

726612

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000574

Gnomad4 NFE exome

AF:

0.000479

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000112

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000199

AC:

ExAC

AF:

0.000121

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.113C>T (p.P38L) alteration is located in exon 2 (coding exon 2) of the PRR3 gene. This alteration results from a C to T substitution at nucleotide position 113, causing the proline (P) at amino acid position 38 to be replaced by a leucine (L). 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

0.34

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Benign

0.72

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.64

MVP

0.86

MPC

1.0

ClinPred

0.48

GERP RS

4.9

Varity_R

0.21

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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