Variant 4-70158740-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_214711.4(PRR27):c.488C>A(p.Pro163His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,578,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PRR27
NM_214711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.452

Variant links:

Genes affected

PRR27 (HGNC:33193): (proline rich 27) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

PRR27 links:

PRR27 (HGNC:):

PRR27 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=0.22739929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR27	NM_214711.4 linkuse as main transcript	c.488C>A	p.Pro163His	missense_variant	3/5	ENST00000344526.10	NP_999876.2	Q6MZM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR27	ENST00000344526.10 linkuse as main transcript	c.488C>A	p.Pro163His	missense_variant	3/5	1	NM_214711.4	ENSP00000343172.5		Q6MZM9

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

146960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250218

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135522

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

6.99e-7

AC:

AN:

1431598

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000136

AC:

AN:

146960

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

71868

show subpopulations

Gnomad4 AFR

AF:

0.0000488

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000840

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.488C>A (p.P163H) alteration is located in exon 3 (coding exon 3) of the PRR27 gene. This alteration results from a C to A substitution at nucleotide position 488, causing the proline (P) at amino acid position 163 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

0.22

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.7

DANN

Benign

0.32

DEOGEN2

Benign

0.059

T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.032

M_CAP

Benign

0.011

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

L;L

PROVEAN

Pathogenic

-7.6

D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.99

D;D

Vest4

0.22

MVP

0.067

MPC

0.032

ClinPred

0.72

GERP RS

-2.6

Varity_R

0.25

gMVP

0.20

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