chr9-96655152-C-T

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

3
6
9

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]

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
PRXL2CNM_153698.2 linkc.130G>A p.Gly44Arg missense_variant Exon 1 of 6 ENST00000375234.8 NP_714542.1 Q7RTV5
PRXL2CXM_005251783.4 linkc.130G>A p.Gly44Arg missense_variant Exon 1 of 5 XP_005251840.1
PRXL2CXM_005251784.5 linkc.30+100G>A intron_variant Intron 1 of 5 XP_005251841.1 B7ZKK1
PRXL2CXM_047422905.1 linkc.30+100G>A intron_variant Intron 1 of 4 XP_047278861.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRXL2CENST00000375234.8 linkc.130G>A p.Gly44Arg missense_variant Exon 1 of 6 1 NM_153698.2 ENSP00000364382.3 Q7RTV5
PRXL2CENST00000446045.1 linkc.51+100G>A intron_variant Intron 1 of 5 1 ENSP00000398933.1 H0Y5J5
PRXL2CENST00000464512.1 linkn.-180G>A upstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.000146
AC:
22
AN:
150880
Hom.:
0
Cov.:
32
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:
2
AN:
6482
Hom.:
0
AF XY:
0.000248
AC XY:
1
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.:
1
Cov.:
31
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:
22
AN:
150880
Hom.:
0
Cov.:
32
AF XY:
0.000109
AC XY:
8
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.:
0
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
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.40
T
Eigen
Benign
0.11
Eigen_PC
Benign
-0.088
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.73
T
M_CAP
Uncertain
0.19
D
MetaRNN
Benign
0.37
T
MetaSVM
Uncertain
-0.22
T
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-7.0
D
REVEL
Uncertain
0.39
Sift
Uncertain
0.016
D
Sift4G
Uncertain
0.028
D
Polyphen
0.99
D
Vest4
0.42
MutPred
0.69
Gain of solvent accessibility (P = 0.0042);
MVP
0.54
MPC
0.17
ClinPred
0.77
D
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.

Other links and lift over

dbSNP: rs1436052953; hg19: chr9-99417434; API