1-2587245-C-T

Variant names:

• chr1-2587245-C-T
• rs1157106971
• NM_152371.5:c.218C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152371.5(PRXL2B):​c.218C>T​(p.Pro73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. P73H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PRXL2B NM_152371.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24569303).

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.218C>T	p.Pro73Leu	missense	Exon 2 of 7	NP_689584.5
	PRXL2B	NM_001195736.3		c.218C>T	p.Pro73Leu	missense	Exon 2 of 7	NP_001182665.4
	PRXL2B	NM_001195737.3		c.218C>T	p.Pro73Leu	missense	Exon 2 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.218C>T	p.Pro73Leu	missense	Exon 2 of 7	ENSP00000394405.4	Q8TBF2-1
	PRXL2B	ENST00000444521.6	TSL:2	c.308C>T	p.Pro103Leu	missense	Exon 2 of 7	ENSP00000413218.3	A0A0A0MT35
	PRXL2B	ENST00000378424.9	TSL:5	c.218C>T	p.Pro73Leu	missense	Exon 2 of 7	ENSP00000367681.5	Q8TBF2-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425926 Hom.: 0 Cov.: 35 AF XY: 0.00000141 AC XY: 1 AN XY: 707834

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32900

American (AMR) AF: 0.00 AC: 0 AN: 41562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25634

East Asian (EAS) AF: 0.00 AC: 0 AN: 38084

South Asian (SAS) AF: 0.00 AC: 0 AN: 82560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100316

Other (OTH) AF: 0.00 AC: 0 AN: 59302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.88	T
PhyloP100		0.80
PrimateAI	Uncertain	0.77	T
REVEL	Benign	0.22
Sift4G	Uncertain	0.049	D
Polyphen		0.59	P
Vest4		0.28
MutPred		0.47		Gain of stability (P = 0.0212)
MVP		0.49
MPC		0.47
ClinPred		0.71	D
GERP RS		3.9
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.40
gMVP		0.71
Mutation Taster		=69/31	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: rs1157106971; hg19: chr1-2518684;