7-29566457-C-A

Variant summary

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

The NM_175887.3(PRR15):​c.128C>A​(p.Thr43Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,599,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRR15
NM_175887.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.955
Variant links:
Genes affected
PRR15 (HGNC:22310): (proline rich 15)

Genome browser will be placed here

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=0.034234613).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRR15NM_175887.3 linkc.128C>A p.Thr43Lys missense_variant Exon 2 of 2 ENST00000319694.3 NP_787083.1 Q8IV56A4D1A1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRR15ENST00000319694.3 linkc.128C>A p.Thr43Lys missense_variant Exon 2 of 2 1 NM_175887.3 ENSP00000317836.2 Q8IV56
PRR15ENST00000450427.1 linkc.*74C>A downstream_gene_variant 2 ENSP00000408158.1 C9JQ22

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
33
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000465
AC:
1
AN:
215042
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
118604
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000619
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1447638
Hom.:
0
Cov.:
65
AF XY:
0.00000278
AC XY:
2
AN XY:
719140
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000770
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
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.128C>A (p.T43K) alteration is located in exon 2 (coding exon 1) of the PRR15 gene. This alteration results from a C to A substitution at nucleotide position 128, causing the threonine (T) at amino acid position 43 to be replaced by a lysine (K). 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
0.16
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
5.3
DANN
Benign
0.94
DEOGEN2
Benign
0.0091
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.034
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.12
N
REVEL
Benign
0.032
Sift
Benign
0.90
T
Sift4G
Benign
0.91
T
Polyphen
0.54
P
Vest4
0.13
MutPred
0.32
Loss of phosphorylation at T43 (P = 0.0015);
MVP
0.014
MPC
0.49
ClinPred
0.062
T
GERP RS
-0.28
Varity_R
0.032
gMVP
0.19

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.

Other links and lift over

dbSNP: rs1283362926; hg19: chr7-29606073; API