9-96655152-C-G

Variant names:

• chr9-96655152-C-G
• rs1436052953
• NM_153698.2:c.130G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153698.2(PRXL2C):​c.130G>C​(p.Gly44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000861 in 1,161,754 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: PRXL2C NM_153698.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 0 publications found

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]

ENSG00000294376 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153698.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRXL2C	NM_153698.2	MANE Select	c.130G>C	p.Gly44Arg	missense	Exon 1 of 6	NP_714542.1	Q7RTV5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRXL2C	ENST00000375234.8	TSL:1 MANE Select	c.130G>C	p.Gly44Arg	missense	Exon 1 of 6	ENSP00000364382.3	Q7RTV5
	PRXL2C	ENST00000446045.1	TSL:1	c.51+100G>C		intron	N/A	ENSP00000398933.1	H0Y5J5
	PRXL2C	ENST00000946150.1		c.130G>C	p.Gly44Arg	missense	Exon 1 of 6	ENSP00000616209.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.61e-7 AC: 1 AN: 1161754 Hom.: 0 Cov.: 31 AF XY: 0.00000177 AC XY: 1 AN XY: 563978

African (AFR) AF: 0.00 AC: 0 AN: 23192

American (AMR) AF: 0.00 AC: 0 AN: 10336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15468

East Asian (EAS) AF: 0.00 AC: 0 AN: 25534

South Asian (SAS) AF: 0.00 AC: 0 AN: 42518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3152

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 968916

Other (OTH) AF: 0.00 AC: 0 AN: 46466

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.072
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.18	T
PhyloP100		1.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.38
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		0.96	D
GERP RS		3.9
PromoterAI		-0.017	Neutral
Varity_R		0.63
gMVP		0.81
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1436052953; hg19: chr9-99417434;