Variant 11-32853507-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024081.6(PRRG4):c.661A>G(p.Met221Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

PRRG4
NM_024081.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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:

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=0.04173538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRG4	NM_024081.6 link	c.661A>G	p.Met221Val	missense_variant	6/6	ENST00000257836.4	NP_076986.1	Q9BZD6A0A0S2Z5N9
PRRG4	XM_006718314.4 link	c.661A>G	p.Met221Val	missense_variant	6/6		XP_006718377.1	Q9BZD6A0A0S2Z5N9
PRRG4	XM_006718313.4 link	c.*75A>G		3_prime_UTR_variant	5/5		XP_006718376.4	A0A0S2Z5M6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRG4	ENST00000257836.4 link	c.661A>G	p.Met221Val	missense_variant	6/6	1	NM_024081.6	ENSP00000257836.3		Q9BZD6

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000839

AC:

AN:

250154

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0000868

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1461092

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000407

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000857

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

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

Jun 07, 2023

The c.661A>G (p.M221V) alteration is located in exon 6 (coding exon 5) of the PRRG4 gene. This alteration results from a A to G substitution at nucleotide position 661, causing the methionine (M) at amino acid position 221 to be replaced by a valine (V). 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

0.097

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.042

MetaSVM

Uncertain

0.50

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.74

REVEL

Uncertain

0.36

Sift

Uncertain

0.012

Sift4G

Uncertain

0.022

Polyphen

0.0020

Vest4

0.24

MVP

0.90

MPC

0.33

ClinPred

0.029

GERP RS

1.9

Varity_R

0.20

gMVP

0.48

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