chr9-96645955-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153698.2(PRXL2C):​c.491G>A​(p.Gly164Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRXL2C
NM_153698.2 missense

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRXL2CNM_153698.2 linkc.491G>A p.Gly164Asp missense_variant Exon 5 of 6 ENST00000375234.8 NP_714542.1 Q7RTV5
PRXL2CXM_005251784.5 linkc.329G>A p.Gly110Asp missense_variant Exon 5 of 6 XP_005251841.1 B7ZKK1
PRXL2CXM_005251783.4 linkc.422-4069G>A intron_variant Intron 4 of 4 XP_005251840.1
PRXL2CXM_047422905.1 linkc.260-4069G>A intron_variant Intron 4 of 4 XP_047278861.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRXL2CENST00000375234.8 linkc.491G>A p.Gly164Asp missense_variant Exon 5 of 6 1 NM_153698.2 ENSP00000364382.3 Q7RTV5
PRXL2CENST00000446045.1 linkc.350G>A p.Gly117Asp missense_variant Exon 5 of 6 1 ENSP00000398933.1 H0Y5J5
PRXL2CENST00000411939.5 linkc.203-4069G>A intron_variant Intron 3 of 3 3 ENSP00000412378.1 H0Y7F1
PRXL2CENST00000464512.1 linkn.*35G>A downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461586
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727098
show subpopulations
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 17, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.491G>A (p.G164D) alteration is located in exon 5 (coding exon 5) of the AAED1 gene. This alteration results from a G to A substitution at nucleotide position 491, causing the glycine (G) at amino acid position 164 to be replaced by an aspartic acid (D). 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
0.67
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0068
T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0067
T
MetaRNN
Uncertain
0.61
D
MetaSVM
Benign
-0.85
T
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.16
Sift
Benign
0.089
T
Sift4G
Benign
0.12
T
Polyphen
0.97
D
Vest4
0.63
MutPred
0.48
Loss of sheet (P = 0.1158);
MVP
0.42
MPC
0.13
ClinPred
0.96
D
GERP RS
5.4
Varity_R
0.54
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-99408237; API