Genetic Variant PRXL2C:p.Gly44Arg (chr9-96655152-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_153698.2(PRXL2C):c.130G>A(p.Gly44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,312,634 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 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

PRXL2C
NM_153698.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

PRXL2C (HGNC:16881): (peroxiredoxin like 2C) Predicted to enable antioxidant activity. Involved in positive regulation of ERK1 and ERK2 cascade and positive regulation of glycolytic process. [provided by Alliance of Genome Resources, Apr 2022]

PRXL2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37246174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRXL2C	NM_153698.2 link	c.130G>A	p.Gly44Arg	missense_variant	Exon 1 of 6	ENST00000375234.8	NP_714542.1	Q7RTV5
PRXL2C	XM_005251783.4 link	c.130G>A	p.Gly44Arg	missense_variant	Exon 1 of 5		XP_005251840.1
PRXL2C	XM_005251784.5 link	c.30+100G>A		intron_variant	Intron 1 of 5		XP_005251841.1	B7ZKK1
PRXL2C	XM_047422905.1 link	c.30+100G>A		intron_variant	Intron 1 of 4		XP_047278861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRXL2C	ENST00000375234.8 link	c.130G>A	p.Gly44Arg	missense_variant	Exon 1 of 6	1	NM_153698.2	ENSP00000364382.3	Q7RTV5
PRXL2C	ENST00000446045.1 link	c.51+100G>A		intron_variant	Intron 1 of 5	1		ENSP00000398933.1	H0Y5J5
PRXL2C	ENST00000464512.1 link	n.-180G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

150880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000309

AC:

AN:

6482

Hom.:

AF XY:

0.000248

AC XY:

AN XY:

4038

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000737

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000211

AC:

245

AN:

1161754

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

123

AN XY:

563978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000967

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000244

Gnomad4 OTH exome

AF:

0.000172

GnomAD4 genome

AF:

0.000146

AC:

AN:

150880

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73678

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000296

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000265

Hom.:

Bravo

AF:

0.000208

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130G>A (p.G44R) alteration is located in exon 1 (coding exon 1) of the AAED1 gene. This alteration results from a G to A substitution at nucleotide position 130, causing the glycine (G) at amino acid position 44 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

Pathogenic

0.85

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Benign

0.11

Eigen_PC

Benign

-0.088

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.37

MetaSVM

Uncertain

-0.22

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.39

Sift

Uncertain

0.016

Sift4G

Uncertain

0.028

Polyphen

0.99

Vest4

0.42

MutPred

0.69

Gain of solvent accessibility (P = 0.0042);

MVP

0.54

MPC

0.17

ClinPred

0.77

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.63

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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