NM_001142395.2:c.401C>G

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.401C>G(p.Pro134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,206,725 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P134Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000017 ( 0 hom. 4 hem. )

Consequence

PRRG1
NM_001142395.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

Publications

2 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=0.27379507).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRG1	NM_001142395.2 link	c.401C>G	p.Pro134Arg	missense_variant	Exon 4 of 4	ENST00000378628.9	NP_001135867.1	O14668-1Q8NEK6
PRRG1	NM_000950.3 link	c.401C>G	p.Pro134Arg	missense_variant	Exon 5 of 5		NP_000941.1	O14668-1Q8NEK6
PRRG1	NM_001173489.2 link	c.401C>G	p.Pro134Arg	missense_variant	Exon 5 of 5		NP_001166960.1	O14668-1
PRRG1	NM_001173490.2 link	c.401C>G	p.Pro134Arg	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.401C>G	p.Pro134Arg	missense_variant	Exon 4 of 4	1	NM_001142395.2	ENSP00000367894.4		O14668-1
ENSG00000250349	ENST00000465127.1 link	c.171+27365C>G		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0000183

AC:

AN:

109248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000381

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000545

AC:

AN:

183353

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:

0.0000173

AC:

AN:

1097477

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

362909

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26391

American (AMR)

AF:

0.00

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19382

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.0000202

AC:

AN:

841434

Other (OTH)

AF:

0.0000217

AC:

AN:

46077

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000183

AC:

AN:

109248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31524

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29914

American (AMR)

AF:

0.00

AC:

AN:

10132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2613

East Asian (EAS)

AF:

0.00

AC:

AN:

3499

South Asian (SAS)

AF:

0.00

AC:

AN:

2430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000381

AC:

AN:

52504

Other (OTH)

AF:

0.00

AC:

AN:

1450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 02, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.401C>G (p.P134R) alteration is located in exon 5 (coding exon 3) of the PRRG1 gene. This alteration results from a C to G substitution at nucleotide position 401, causing the proline (P) at amino acid position 134 to be replaced by an arginine (R). 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

0.098

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T;T;T;T

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.73

.;T;.;T;.

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

1.4

L;.;L;L;L

PhyloP100

2.6

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.19

N;N;N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.17

T;D;T;T;T

Sift4G

Uncertain

0.025

D;D;D;D;D

Polyphen

0.082

B;.;B;B;B

Vest4

0.40

MutPred

0.37

Gain of solvent accessibility (P = 0.0026);Gain of solvent accessibility (P = 0.0026);Gain of solvent accessibility (P = 0.0026);Gain of solvent accessibility (P = 0.0026);Gain of solvent accessibility (P = 0.0026);

MVP

0.47

MPC

0.45

ClinPred

0.43

GERP RS

5.3

Varity_R

0.10

gMVP

0.49

Mutation Taster

=87/13

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.

NM_001142395.2:c.401C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over