NM_032333.5:c.519C>T

Variant names:

• chr10-80427439-C-T
• rs1271302688
• NM_032333.5:c.519C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_032333.5(PRXL2A):​c.519C>T​(p.Asn173Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRXL2A NM_032333.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 0 publications found

Genes affected

PRXL2A (HGNC:28651): (peroxiredoxin like 2A) Enables antioxidant activity. Involved in regulation of osteoclast differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032333.5. 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
	PRXL2A	NM_032333.5	MANE Select	c.519C>T	p.Asn173Asn	synonymous	Exon 5 of 6	NP_115709.3
	PRXL2A	NM_001243778.2		c.519C>T	p.Asn173Asn	synonymous	Exon 5 of 6	NP_001230707.1	Q9BRX8-1
	PRXL2A	NM_001243779.2		c.519C>T	p.Asn173Asn	synonymous	Exon 5 of 6	NP_001230708.1	Q9BRX8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRXL2A	ENST00000606162.6	TSL:1 MANE Select	c.519C>T	p.Asn173Asn	synonymous	Exon 5 of 6	ENSP00000482445.1	Q9BRX8-1
	PRXL2A	ENST00000372187.9	TSL:1	c.519C>T	p.Asn173Asn	synonymous	Exon 5 of 6	ENSP00000361261.5	Q9BRX8-1
	PRXL2A	ENST00000372181.1	TSL:2	c.519C>T	p.Asn173Asn	synonymous	Exon 4 of 5	ENSP00000361254.1	Q9BRX8-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

⚠️ 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: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ 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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.2
DANN	Benign	0.68
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1271302688; hg19: chr10-82187195;