Variant 2-27137561-G-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 ENST00000335524.7(PRR30):c.769C>T(p.Arg257Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,591,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

PRR30
ENST00000335524.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

PRR30 (HGNC:28677): (proline rich 30)

PRR30 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=0.11642477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR30	NM_178553.4 linkuse as main transcript	c.769C>T	p.Arg257Trp	missense_variant	3/3	ENST00000335524.7	NP_848648.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR30	ENST00000335524.7 linkuse as main transcript	c.769C>T	p.Arg257Trp	missense_variant	3/3	1	NM_178553.4	ENSP00000335017	P1
PRR30	ENST00000432962.2 linkuse as main transcript	c.275C>T	p.Pro92Leu	missense_variant	4/4	3		ENSP00000393468

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000747

AC:

AN:

227666

Hom.:

AF XY:

0.0000643

AC XY:

AN XY:

124350

show subpopulations

Gnomad AFR exome

AF:

0.000603

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000380

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000731

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000297

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000771

AC:

111

AN:

1438892

Hom.:

Cov.:

AF XY:

0.0000827

AC XY:

AN XY:

713078

show subpopulations

Gnomad4 AFR exome

AF:

0.00115

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000532

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000382

Gnomad4 OTH exome

AF:

0.000135

GnomAD4 genome

AF:

0.000197

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000744

Hom.:

Bravo

AF:

0.000257

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000240

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.0000830

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 15, 2021

The c.769C>T (p.R257W) alteration is located in exon 3 (coding exon 1) of the PRR30 gene. This alteration results from a C to T substitution at nucleotide position 769, causing the arginine (R) at amino acid position 257 to be replaced by a tryptophan (W). 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

0.25

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

0.0099

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.22

M_CAP

Benign

0.0073

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-10

REVEL

Benign

0.12

MVP

0.30

ClinPred

0.25

GERP RS

2.6

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