Genetic Variant PRR3:p.Pro34Thr (chr6-30557444-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025263.4(PRR3):c.100C>A(p.Pro34Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRR3
NM_025263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.742

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12691134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR3	NM_025263.4 link	c.100C>A	p.Pro34Thr	missense_variant	Exon 1 of 4	ENST00000376560.8	NP_079539.2	P79522-1Q96QB9
PRR3	NM_001077497.3 link	c.100C>A	p.Pro34Thr	missense_variant	Exon 1 of 3		NP_001070965.1	B3KQA4
PRR3	XM_047419381.1 link	c.258C>A	p.Val86Val	synonymous_variant	Exon 1 of 3		XP_047275337.1
PRR3	XM_047419382.1 link	c.258C>A	p.Val86Val	synonymous_variant	Exon 1 of 2		XP_047275338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR3	ENST00000376560.8 link	c.100C>A	p.Pro34Thr	missense_variant	Exon 1 of 4	1	NM_025263.4	ENSP00000365744.4		P79522-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455548

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724106

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.100C>A (p.P34T) alteration is located in exon 1 (coding exon 1) of the PRR3 gene. This alteration results from a C to A substitution at nucleotide position 100, causing the proline (P) at amino acid position 34 to be replaced by a threonine (T). 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

0.083

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

T;.

Eigen

Benign

-0.011

Eigen_PC

Benign

0.048

FATHMM_MKL

Benign

0.060

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.088

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.050

T;D

Polyphen

0.54

P;P

Vest4

0.33

MutPred

0.18

Gain of glycosylation at P34 (P = 0.0024);Gain of glycosylation at P34 (P = 0.0024);

MVP

0.50

MPC

1.2

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.073

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over