9-96641849-C-A

Variant names:

• chr9-96641849-C-A
• rs140240239
• NM_153698.2:c.591G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153698.2(PRXL2C):​c.591G>T​(p.Arg197Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000543 in 1,541,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: PRXL2C NM_153698.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.431
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16695574).

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.591G>T	p.Arg197Ser	missense	Exon 6 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.591G>T	p.Arg197Ser	missense	Exon 6 of 6	ENSP00000364382.3	Q7RTV5
	PRXL2C	ENST00000446045.1	TSL:1	c.450G>T	p.Arg150Ser	missense	Exon 6 of 6	ENSP00000398933.1	H0Y5J5
	PRXL2C	ENST00000946150.1		c.585G>T	p.Arg195Ser	missense	Exon 6 of 6	ENSP00000616209.1

Frequencies

GnomAD3 genomes AF: 0.000513 AC: 78 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000999

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000363 AC: 88 AN: 242410 AF XY: 0.000304

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000749

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.000546 AC: 759 AN: 1388906 Hom.: 1 Cov.: 30 AF XY: 0.000531 AC XY: 364 AN XY: 685440

African (AFR) AF: 0.0000619 AC: 2 AN: 32302

American (AMR) AF: 0.0000234 AC: 1 AN: 42682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24528

East Asian (EAS) AF: 0.00 AC: 0 AN: 38100

South Asian (SAS) AF: 0.00 AC: 0 AN: 76372

European-Finnish (FIN) AF: 0.0000980 AC: 5 AN: 51010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.000693 AC: 736 AN: 1061904

Other (OTH) AF: 0.000265 AC: 15 AN: 56510

GnomAD4 genome AF: 0.000513 AC: 78 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74330

African (AFR) AF: 0.000169 AC: 7 AN: 41440

American (AMR) AF: 0.000131 AC: 2 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000999 AC: 68 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000621 Hom.: 1

Bravo AF: 0.000400

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000404 AC: 49

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.68	T
PhyloP100		-0.43
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.24
Sift	Benign	0.098	T
Sift4G	Benign	0.19	T
Polyphen		0.37	B
Vest4		0.66
MutPred		0.64		Gain of methylation at K201 (P = 0.0457)
MVP		0.22
MPC		0.034
ClinPred		0.052	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.78
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs140240239; hg19: chr9-99404131;