Variant chr11-32830626-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024081.6(PRRG4):c.97G>A(p.Glu33Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,612,056 control chromosomes in the GnomAD database, including 12,750 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.10 ( 840 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11910 hom. )

Consequence

PRRG4
NM_024081.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.370

Variant links:

Genes affected

PRRG4 (HGNC:30799): (proline rich and Gla domain 4) Enables WW domain binding activity. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PRRG4 links:

CCDC73 (HGNC:):

CCDC73 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015422106).

BP6

Variant 11-32830626-G-A is Benign according to our data. Variant chr11-32830626-G-A is described in ClinVar as [Benign]. Clinvar id is 3059407.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRRG4	NM_024081.6 linkuse as main transcript	c.97G>A	p.Glu33Lys	missense_variant	2/6	ENST00000257836.4
PRRG4	XM_006718314.4 linkuse as main transcript	c.97G>A	p.Glu33Lys	missense_variant	2/6
PRRG4	XM_006718313.4 linkuse as main transcript	c.97G>A	p.Glu33Lys	missense_variant	2/5
CCDC73	XM_047427029.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRG4	ENST00000257836.4 linkuse as main transcript	c.97G>A	p.Glu33Lys	missense_variant	2/6	1	NM_024081.6	P1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15491

AN:

152062

Hom.:

839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0792

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0544

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.0936

GnomAD3 exomes

AF:

0.104

AC:

26032

AN:

250386

Hom.:

1710

AF XY:

0.107

AC XY:

14523

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.0773

Gnomad AMR exome

AF:

0.0389

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.122

AC:

178066

AN:

1459876

Hom.:

11910

Cov.:

AF XY:

0.122

AC XY:

88677

AN XY:

726204

show subpopulations

Gnomad4 AFR exome

AF:

0.0779

Gnomad4 AMR exome

AF:

0.0410

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.102

AC:

15495

AN:

152180

Hom.:

840

Cov.:

AF XY:

0.102

AC XY:

7553

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0792

Gnomad4 AMR

AF:

0.0543

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.0926

Alfa

AF:

0.119

Hom.:

1986

Bravo

AF:

0.0949

TwinsUK

AF:

0.128

AC:

475

ALSPAC

AF:

0.132

AC:

507

ESP6500AA

AF:

0.0747

AC:

329

ESP6500EA

AF:

0.122

AC:

1049

ExAC

AF:

0.107

AC:

13052

Asia WGS

AF:

0.0450

AC:

158

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PRRG4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0030

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.99

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.40

REVEL

Benign

0.22

Sift

Benign

0.50

Sift4G

Benign

0.85

Polyphen

0.0010

Vest4

0.077

MPC

0.33

ClinPred

0.0033

GERP RS

2.8

Varity_R

0.041

gMVP

0.76

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