Variant 9-96641849-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153698.2(PRXL2C):c.591G>T(p.Arg197Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000543 in 1,541,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 1 hom. )

Consequence

PRXL2C
NM_153698.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.431

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16695574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRXL2C	NM_153698.2 link	c.591G>T	p.Arg197Ser	missense_variant	6/6	ENST00000375234.8	NP_714542.1	Q7RTV5
PRXL2C	XM_005251783.4 link	c.459G>T	p.Arg153Ser	missense_variant	5/5		XP_005251840.1
PRXL2C	XM_005251784.5 link	c.429G>T	p.Arg143Ser	missense_variant	6/6		XP_005251841.1	B7ZKK1
PRXL2C	XM_047422905.1 link	c.297G>T	p.Arg99Ser	missense_variant	5/5		XP_047278861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRXL2C	ENST00000375234.8 link	c.591G>T	p.Arg197Ser	missense_variant	6/6	1	NM_153698.2	ENSP00000364382.3	Q7RTV5
PRXL2C	ENST00000446045.1 link	c.450G>T	p.Arg150Ser	missense_variant	6/6	1		ENSP00000398933.1	H0Y5J5
PRXL2C	ENST00000411939.5 link	c.240G>T	p.Arg80Ser	missense_variant	4/4	3		ENSP00000412378.1	H0Y7F1

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000999

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000363

AC:

AN:

242410

Hom.:

AF XY:

0.000304

AC XY:

AN XY:

131500

show subpopulations

Gnomad AFR exome

AF:

0.000194

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:

0.0000465

Gnomad NFE exome

AF:

0.000749

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000546

AC:

759

AN:

1388906

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

364

AN XY:

685440

show subpopulations

Gnomad4 AFR exome

AF:

0.0000619

Gnomad4 AMR exome

AF:

0.0000234

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000980

Gnomad4 NFE exome

AF:

0.000693

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000513

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000999

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000613

Hom.:

Bravo

AF:

0.000400

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000404

AC:

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

Aug 13, 2021

The c.591G>T (p.R197S) alteration is located in exon 6 (coding exon 6) of the AAED1 gene. This alteration results from a G to T substitution at nucleotide position 591, causing the arginine (R) at amino acid position 197 to be replaced by a serine (S). 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

0.80

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.020

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.68

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.0

REVEL

Benign

0.24

Sift

Benign

0.098

Sift4G

Benign

0.19

Polyphen

0.37

Vest4

0.66

MutPred

0.64

Gain of methylation at K201 (P = 0.0457);

MVP

0.22

MPC

0.034

ClinPred

0.052

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.78

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