chr9-96655110-C-T

Variant summary

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

The NM_153698.2(PRXL2C):​c.172G>A​(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PRXL2C
NM_153698.2 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2227422).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRXL2CNM_153698.2 linkc.172G>A p.Ala58Thr missense_variant Exon 1 of 6 ENST00000375234.8 NP_714542.1 Q7RTV5
PRXL2CXM_005251783.4 linkc.172G>A p.Ala58Thr missense_variant Exon 1 of 5 XP_005251840.1
PRXL2CXM_005251784.5 linkc.30+142G>A intron_variant Intron 1 of 5 XP_005251841.1 B7ZKK1
PRXL2CXM_047422905.1 linkc.30+142G>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.172G>A p.Ala58Thr missense_variant Exon 1 of 6 1 NM_153698.2 ENSP00000364382.3 Q7RTV5
PRXL2CENST00000446045.1 linkc.51+142G>A intron_variant Intron 1 of 5 1 ENSP00000398933.1 H0Y5J5
PRXL2CENST00000464512.1 linkn.-138G>A upstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151756
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1280046
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
630404
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151756
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74122
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.172G>A (p.A58T) 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 172, causing the alanine (A) at amino acid position 58 to be replaced by a threonine (T). 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
0.14
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0040
T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.050
N
REVEL
Benign
0.11
Sift
Benign
0.56
T
Sift4G
Benign
0.27
T
Polyphen
0.96
D
Vest4
0.30
MutPred
0.49
Gain of sheet (P = 0.039);
MVP
0.29
MPC
0.024
ClinPred
0.65
D
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.035
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs1848336071; hg19: chr9-99417392; API