Genetic Variant PRR15:p.Pro71His (chr7-29566541-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_175887.3(PRR15):c.212C>A(p.Pro71His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,607,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

PRR15
NM_175887.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.514

Variant links:

Genes affected

PRR15 (HGNC:22310): (proline rich 15)

PRR15 links:

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=0.056628466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR15	NM_175887.3 link	c.212C>A	p.Pro71His	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
PRR15	ENST00000319694.3 link	c.212C>A	p.Pro71His	missense_variant	Exon 2 of 2	1	NM_175887.3	ENSP00000317836.2		Q8IV56
PRR15	ENST00000450427.1 link	c.*158C>A		downstream_gene_variant		2		ENSP00000408158.1		C9JQ22

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

231406

Hom.:

AF XY:

0.0000863

AC XY:

AN XY:

127414

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000325

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000492

Gnomad NFE exome

AF:

0.000217

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000247

AC:

359

AN:

1455668

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

178

AN XY:

723774

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000271

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:

0.000296

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

AF:

0.000230

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000264

Hom.:

Bravo

AF:

0.000204

ExAC

AF:

0.0000663

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.212C>A (p.P71H) 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 212, causing the proline (P) at amino acid position 71 to be replaced by a histidine (H). 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

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.44

M_CAP

Benign

0.026

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.75

REVEL

Benign

0.044

Sift

Benign

0.033

Sift4G

Uncertain

0.023

Polyphen

0.97

Vest4

0.14

MVP

0.22

MPC

1.1

ClinPred

0.058

GERP RS

3.3

Varity_R

0.058

gMVP

0.11

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