X-37453449-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001142395.2(PRRG1):c.485G>A(p.Arg162His) variant causes a missense change. The variant allele was found at a frequency of 0.0000664 in 1,205,474 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., 3 hem., cov: 21)

Exomes 𝑓: 0.000067 ( 0 hom. 21 hem. )

Consequence

PRRG1
NM_001142395.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

Publications

1 publications found

Variant links:

Genes affected

PRRG1 (HGNC:9469): (proline rich and Gla domain 1) This gene encodes a vitamin K-dependent, gamma-carboxyglutamic acid (Gla)-containing, single-pass transmembrane protein. This protein contains a Gla domain at the N-terminus, preceded by a propeptide sequence required for post-translational gamma-carboxylation of specific glutamic acid residues by a vitamin K-dependent gamma-carboxylase. The C-terminus is proline-rich containing PPXY and PXXP motifs found in a variety of signaling and cytoskeletal proteins. This gene is highly expressed in the spinal cord. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]

PRRG1 links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34564608).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRG1	NM_001142395.2 link	c.485G>A	p.Arg162His	missense_variant	Exon 4 of 4	ENST00000378628.9	NP_001135867.1	O14668-1Q8NEK6
PRRG1	NM_000950.3 link	c.485G>A	p.Arg162His	missense_variant	Exon 5 of 5		NP_000941.1	O14668-1Q8NEK6
PRRG1	NM_001173489.2 link	c.485G>A	p.Arg162His	missense_variant	Exon 5 of 5		NP_001166960.1	O14668-1
PRRG1	NM_001173490.2 link	c.485G>A	p.Arg162His	missense_variant	Exon 4 of 4		NP_001166961.1	O14668-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRG1	ENST00000378628.9 link	c.485G>A	p.Arg162His	missense_variant	Exon 4 of 4	1	NM_001142395.2	ENSP00000367894.4		O14668-1
ENSG00000250349	ENST00000465127.1 link	c.171+27449G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0000557

AC:

AN:

107647

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000683

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000289

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000574

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000546

AC:

AN:

183276

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000674

AC:

AN:

1097827

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363197

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26391

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00146

AC:

AN:

30202

South Asian (SAS)

AF:

0.00

AC:

AN:

54127

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000345

AC:

AN:

841780

Other (OTH)

AF:

0.00

AC:

AN:

46081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000557

AC:

AN:

107647

Hom.:

Cov.:

AF XY:

0.0000989

AC XY:

AN XY:

30327

show subpopulations

African (AFR)

AF:

0.0000683

AC:

AN:

29275

American (AMR)

AF:

0.00

AC:

AN:

9890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2602

East Asian (EAS)

AF:

0.000289

AC:

AN:

3459

South Asian (SAS)

AF:

0.00

AC:

AN:

2396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.0000574

AC:

AN:

52224

Other (OTH)

AF:

0.00

AC:

AN:

1429

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.485G>A (p.R162H) alteration is located in exon 5 (coding exon 3) of the PRRG1 gene. This alteration results from a G to A substitution at nucleotide position 485, causing the arginine (R) at amino acid position 162 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

0.10

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.29

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;T;T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

.;.;D;.

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.1

M;M;M;M

PhyloP100

4.7

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Pathogenic

0.73

Sift

Benign

0.040

D;D;D;D

Sift4G

Benign

0.062

T;T;T;T

Polyphen

0.96

D;D;D;D

Vest4

0.19

MutPred

0.41

Loss of methylation at R162 (P = 0.0638);Loss of methylation at R162 (P = 0.0638);Loss of methylation at R162 (P = 0.0638);Loss of methylation at R162 (P = 0.0638);

MVP

0.72

MPC

0.82

ClinPred

0.52

GERP RS

6.0

Varity_R

0.46

gMVP

0.60

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-37453449-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over