Genetic Variant PRRG1:p.Pro134Ser (chrX-37453364-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142395.2(PRRG1):c.400C>T(p.Pro134Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,494 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P134R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

PRRG1
NM_001142395.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22035775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRG1	NM_001142395.2 link	c.400C>T	p.Pro134Ser	missense_variant	Exon 4 of 4	ENST00000378628.9	NP_001135867.1	O14668-1Q8NEK6
PRRG1	NM_000950.3 link	c.400C>T	p.Pro134Ser	missense_variant	Exon 5 of 5		NP_000941.1	O14668-1Q8NEK6
PRRG1	NM_001173489.2 link	c.400C>T	p.Pro134Ser	missense_variant	Exon 5 of 5		NP_001166960.1	O14668-1
PRRG1	NM_001173490.2 link	c.400C>T	p.Pro134Ser	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.400C>T	p.Pro134Ser	missense_variant	Exon 4 of 4	1	NM_001142395.2	ENSP00000367894.4		O14668-1
ENSG00000250349	ENST00000465127.1 link	c.171+27364C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097494

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26388

American (AMR)

AF:

0.00

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19378

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54125

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40529

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841455

Other (OTH)

AF:

0.00

AC:

AN:

46075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.034

T;T;T;T;T

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.77

.;T;.;T;.

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Uncertain

0.65

MutationAssessor

Benign

1.4

L;.;L;L;L

PhyloP100

1.3

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.48

N;N;N;N;N

REVEL

Uncertain

0.41

Sift

Benign

0.20

T;D;T;T;T

Sift4G

Benign

0.24

T;D;T;T;T

Polyphen

0.025

B;.;B;B;B

Vest4

0.30

MutPred

0.32

Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);

MVP

0.48

MPC

0.34

ClinPred

0.17

GERP RS

4.3

Varity_R

0.086

gMVP

0.45

Mutation Taster

=92/8

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-37453364-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over