rs5891410

chr8-51372094-CA-Cchr8-51372094-CA-CAAchr8-51372094-CA-CAAAchr8-51372094-CA-CAAAAchr8-51372094-CA-CAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144651.5(PXDNL):c.3693-14del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,129,500 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PXDNL NM_144651.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

Genes affected

PXDNL (HGNC:26359): (peroxidasin like) Predicted to enable heme binding activity and peroxidase activity. Predicted to be involved in hydrogen peroxide catabolic process. Predicted to be located in cytoplasm. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXDNL	NM_144651.5	c.3693-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000356297.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXDNL	ENST00000356297.5	c.3693-14del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_144651.5	P1
PXDNL	ENST00000522933.5	c.914-14del		splice_polypyrimidine_tract_variant, intron_variant		5
PXDNL	ENST00000522628.5	c.1491-14del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 148924 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

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: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000754 AC: 79 AN: 104804 Hom.: 0 AF XY: 0.000795 AC XY: 44 AN XY: 55320

Gnomad AFR exome AF: 0.00400

Gnomad AMR exome AF: 0.000250

Gnomad ASJ exome AF: 0.000354

Gnomad EAS exome AF: 0.00103

Gnomad SAS exome AF: 0.000470

Gnomad FIN exome AF: 0.000270

Gnomad NFE exome AF: 0.000777

Gnomad OTH exome AF: 0.000677

GnomAD4 exome AF: 0.000158 AC: 179 AN: 1129500 Hom.: 0 Cov.: 28 AF XY: 0.000129 AC XY: 72 AN XY: 559626

Gnomad4 AFR exome AF: 0.00126

Gnomad4 AMR exome AF: 0.000239

Gnomad4 ASJ exome AF: 0.0000958

Gnomad4 EAS exome AF: 0.0000325

Gnomad4 SAS exome AF: 0.000134

Gnomad4 FIN exome AF: 0.0000488

Gnomad4 NFE exome AF: 0.000130

Gnomad4 OTH exome AF: 0.000207

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 148924 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72556

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00216 Hom.: 1994

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs5891410; hg19: chr8-52284654;