chr1-2586905-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152371.5(PRXL2B):​c.20C>T​(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000648 in 1,311,544 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (1 hom.)
• Consequence: PRXL2B NM_152371.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057178944).

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>T	p.Ala7Val	missense	Exon 1 of 7	NP_689584.5
	PRXL2B	NM_001195736.3		c.20C>T	p.Ala7Val	missense	Exon 1 of 7	NP_001182665.4
	PRXL2B	NM_001195737.3		c.20C>T	p.Ala7Val	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>T	p.Ala7Val	missense	Exon 1 of 7	ENSP00000394405.4	Q8TBF2-1
	PRXL2B	ENST00000444521.6	TSL:2	c.110C>T	p.Ala37Val	missense	Exon 1 of 7	ENSP00000413218.3	A0A0A0MT35
	PRXL2B	ENST00000378424.9	TSL:5	c.20C>T	p.Ala7Val	missense	Exon 1 of 7	ENSP00000367681.5	Q8TBF2-7

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000839 AC: 3 AN: 35750 AF XY: 0.000108

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: 0.000155

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000664 AC: 77 AN: 1159380 Hom.: 1 Cov.: 38 AF XY: 0.0000740 AC XY: 41 AN XY: 553810

African (AFR) AF: 0.00 AC: 0 AN: 24294

American (AMR) AF: 0.000100 AC: 1 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: 0.0000628 AC: 2 AN: 31842

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

Middle Eastern (MID) AF: 0.00213 AC: 7 AN: 3294

European-Non Finnish (NFE) AF: 0.0000633 AC: 61 AN: 964114

Other (OTH) AF: 0.000127 AC: 6 AN: 47328

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.0000855 AC: 9

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	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.24
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.038
Sift	Benign	0.50	T
Sift4G	Uncertain	0.020	D
Polyphen		0.0090	B
Vest4		0.19
MVP		0.34
MPC		0.49
ClinPred		0.050	T
GERP RS		-0.64
PromoterAI		0.034	Neutral
Varity_R		0.073
gMVP		0.17
Mutation Taster		=99/1	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;