rs375491063

Variant names:

• chr1-2586905-C-A
• rs375491063
• NM_152371.5:c.20C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2586905-C-A
• chr1-2586905-C-T

Variant summary

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

The NM_152371.5(PRXL2B):​c.20C>A​(p.Ala7Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,311,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: PRXL2B NM_152371.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 0 publications found

Genes affected

PRXL2B (HGNC:28390): (peroxiredoxin like 2B) Predicted to enable antioxidant activity and prostaglandin-F synthase activity. Predicted to be involved in prostaglandin biosynthetic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12529525).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152371.5. 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
	PRXL2B	NM_152371.5	MANE Select	c.20C>A	p.Ala7Asp	missense	Exon 1 of 7	NP_689584.5
	PRXL2B	NM_001195736.3		c.20C>A	p.Ala7Asp	missense	Exon 1 of 7	NP_001182665.4
	PRXL2B	NM_001195737.3		c.20C>A	p.Ala7Asp	missense	Exon 1 of 7	NP_001182666.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRXL2B	ENST00000419916.8	TSL:1 MANE Select	c.20C>A	p.Ala7Asp	missense	Exon 1 of 7	ENSP00000394405.4	Q8TBF2-1
	PRXL2B	ENST00000444521.6	TSL:2	c.110C>A	p.Ala37Asp	missense	Exon 1 of 7	ENSP00000413218.3	A0A0A0MT35
	PRXL2B	ENST00000378424.9	TSL:5	c.20C>A	p.Ala7Asp	missense	Exon 1 of 7	ENSP00000367681.5	Q8TBF2-7

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000280 AC: 1 AN: 35750 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000517

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 23 AN: 1159380 Hom.: 0 Cov.: 38 AF XY: 0.0000144 AC XY: 8 AN XY: 553810

African (AFR) AF: 0.000247 AC: 6 AN: 24294

American (AMR) AF: 0.00 AC: 0 AN: 9976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15436

East Asian (EAS) AF: 0.00 AC: 0 AN: 28572

South Asian (SAS) AF: 0.00 AC: 0 AN: 31842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34524

Middle Eastern (MID) AF: 0.00121 AC: 4 AN: 3294

European-Non Finnish (NFE) AF: 0.0000114 AC: 11 AN: 964114

Other (OTH) AF: 0.0000423 AC: 2 AN: 47328

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74428

African (AFR) AF: 0.0000241 AC: 1 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000950 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.24
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.096
Sift	Benign	0.20	T
Sift4G	Benign	0.095	T
Polyphen		0.0020	B
Vest4		0.33
MutPred		0.40		Loss of MoRF binding (P = 0.0416)
MVP		0.42
MPC		0.69
ClinPred		0.045	T
GERP RS		-0.64
PromoterAI		0.065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.21
gMVP		0.38
Mutation Taster		=95/5	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: rs375491063; hg19: chr1-2518344;