chr9-96645955-C-T

Variant names:

• chr9-96645955-C-T
• NM_153698.2:c.491G>A

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75

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]

ACMG classification

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
PRXL2C	NM_153698.2	c.491G>A	p.Gly164Asp	missense_variant	Exon 5 of 6	ENST00000375234.8	NP_714542.1
PRXL2C	XM_005251784.5	c.329G>A	p.Gly110Asp	missense_variant	Exon 5 of 6		XP_005251841.1
PRXL2C	XM_005251783.4	c.422-4069G>A		intron_variant	Intron 4 of 4		XP_005251840.1
PRXL2C	XM_047422905.1	c.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
PRXL2C	ENST00000375234.8	c.491G>A	p.Gly164Asp	missense_variant	Exon 5 of 6	1	NM_153698.2	ENSP00000364382.3
PRXL2C	ENST00000446045.1	c.350G>A	p.Gly117Asp	missense_variant	Exon 5 of 6	1		ENSP00000398933.1
PRXL2C	ENST00000411939.5	c.203-4069G>A		intron_variant	Intron 3 of 3	3		ENSP00000412378.1
PRXL2C	ENST00000464512.1	n.*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

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

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;