6-30558156-C-T

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

2
5
11

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]

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
PRR3NM_025263.4 linkc.113C>T p.Pro38Leu missense_variant Exon 2 of 4 ENST00000376560.8 NP_079539.2 P79522-1Q96QB9
PRR3XM_047419381.1 linkc.271C>T p.Pro91Ser missense_variant Exon 2 of 3 XP_047275337.1
PRR3NM_001077497.3 linkc.106+706C>T intron_variant Intron 1 of 2 NP_001070965.1 B3KQA4
PRR3XM_047419382.1 linkc.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
PRR3ENST00000376560.8 linkc.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:
17
AN:
152172
Hom.:
0
Cov.:
32
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:
29
AN:
244676
Hom.:
0
AF XY:
0.000127
AC XY:
17
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.:
0
Cov.:
30
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:
17
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
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.:
0
Bravo
AF:
0.000121
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000199
AC:
1
ExAC
AF:
0.000121
AC:
14
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
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.086
T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Benign
0.72
D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.64
D
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-4.4
D
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.10
T
Polyphen
1.0
D
Vest4
0.64
MVP
0.86
MPC
1.0
ClinPred
0.48
T
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.

Other links and lift over

dbSNP: rs199690651; hg19: chr6-30525933; API