Variant chr9-129719278-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_016307.4(PRRX2):c.307A>C(p.Lys103Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,609,498 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

PRRX2
NM_016307.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33866125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX2	NM_016307.4 linkuse as main transcript	c.307A>C	p.Lys103Gln	missense_variant	2/4	ENST00000372469.6	NP_057391.1	Q99811A0A140VJS2
PRRX2	XM_017014803.1 linkuse as main transcript	c.127A>C	p.Lys43Gln	missense_variant	2/4		XP_016870292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRX2	ENST00000372469.6 linkuse as main transcript	c.307A>C	p.Lys103Gln	missense_variant	2/4	1	NM_016307.4	ENSP00000361547.4		Q99811

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000417

AC:

101

AN:

242452

Hom.:

AF XY:

0.000446

AC XY:

AN XY:

132306

show subpopulations

Gnomad AFR exome

AF:

0.000196

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000500

Gnomad SAS exome

AF:

0.000865

Gnomad FIN exome

AF:

0.0000963

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.000844

GnomAD4 exome

AF:

0.000259

AC:

377

AN:

1457156

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

208

AN XY:

724688

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000607

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.0000383

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000295

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000380

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 23, 2024

The c.307A>C (p.K103Q) alteration is located in exon 2 (coding exon 2) of the PRRX2 gene. This alteration results from a A to C substitution at nucleotide position 307, causing the lysine (K) at amino acid position 103 to be replaced by a glutamine (Q). 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.62

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.73

MVP

0.93

MPC

1.3

ClinPred

0.083

GERP RS

4.4

Varity_R

0.57

gMVP

0.90

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