Variant 9-129665876-C-A 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_016307.4(PRRX2):c.9C>A(p.Ser3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,067,092 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

PRRX2
NM_016307.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

PRRX2 (HGNC:21338): (paired related homeobox 2) The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins. Expression is localized to proliferating fetal fibroblasts and the developing dermal layer, with downregulated expression in adult skin. Increases in expression of this gene during fetal but not adult wound healing suggest a possible role in mechanisms that control mammalian dermal regeneration and prevent formation of scar response to wounding. The expression patterns provide evidence consistent with a role in fetal skin development and a possible role in cellular proliferation. [provided by RefSeq, Jul 2008]

PRRX2 links:

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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=0.05901268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX2	NM_016307.4 linkuse as main transcript	c.9C>A	p.Ser3Arg	missense_variant	1/4	ENST00000372469.6	NP_057391.1	Q99811A0A140VJS2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRX2	ENST00000372469.6 linkuse as main transcript	c.9C>A	p.Ser3Arg	missense_variant	1/4	1	NM_016307.4	ENSP00000361547.4		Q99811

Frequencies

GnomAD3 genomes

AF:

0.000202

AC:

AN:

148786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000668

Gnomad ASJ

AF:

0.00381

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000210

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000167

AC:

153

AN:

918306

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

436180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00501

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.000472

GnomAD4 genome

AF:

0.000202

AC:

AN:

148786

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

AN XY:

72510

show subpopulations

Gnomad4 AFR

AF:

0.0000487

Gnomad4 AMR

AF:

0.0000668

Gnomad4 ASJ

AF:

0.00381

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000210

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000204

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 27, 2022

The c.9C>A (p.S3R) alteration is located in exon 1 (coding exon 1) of the PRRX2 gene. This alteration results from a C to A substitution at nucleotide position 9, causing the serine (S) at amino acid position 3 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

0.31

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.43

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.34

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

0.030

Vest4

0.27

MutPred

0.23

Loss of glycosylation at S3 (P = 0.0107);

MVP

0.85

MPC

0.47

ClinPred

0.52

GERP RS

1.4

Varity_R

0.19

gMVP

0.38

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