8-51320805-G-A

Variant names:

• chr8-51320805-G-A
• rs180687856
• NM_144651.5:c.4239C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_144651.5(PXDNL):​c.4239C>T​(p.Asp1413Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,613,758 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: PXDNL NM_144651.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

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]

ENSG00000253664 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.049).
• BP6: Variant 8-51320805-G-A is Benign according to our data. Variant chr8-51320805-G-A is described in ClinVar as Benign. ClinVar VariationId is 716090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144651.5. 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
	PXDNL	NM_144651.5	MANE Select	c.4239C>T	p.Asp1413Asp	synonymous	Exon 22 of 23	NP_653252.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDNL	ENST00000356297.5	TSL:1 MANE Select	c.4239C>T	p.Asp1413Asp	synonymous	Exon 22 of 23	ENSP00000348645.4	A1KZ92-1
	PXDNL	ENST00000894552.1		c.4419C>T	p.Asp1473Asp	synonymous	Exon 23 of 24	ENSP00000564611.1
	PXDNL	ENST00000894549.1		c.4167C>T	p.Asp1389Asp	synonymous	Exon 21 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152228 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000363 AC: 90 AN: 248268 AF XY: 0.000282

Gnomad AFR exome AF: 0.00546

Gnomad AMR exome AF: 0.0000872

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000161 AC: 236 AN: 1461412 Hom.: 1 Cov.: 30 AF XY: 0.000142 AC XY: 103 AN XY: 727006

African (AFR) AF: 0.00580 AC: 194 AN: 33446

American (AMR) AF: 0.000157 AC: 7 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111654

Other (OTH) AF: 0.000414 AC: 25 AN: 60368

GnomAD4 genome AF: 0.00161 AC: 246 AN: 152346 Hom.: 1 Cov.: 33 AF XY: 0.00141 AC XY: 105 AN XY: 74498

African (AFR) AF: 0.00551 AC: 229 AN: 41578

American (AMR) AF: 0.000653 AC: 10 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000850 Hom.: 0

Bravo AF: 0.00169

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PXDNL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.8
DANN	Benign	0.56
PhyloP100		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs180687856; hg19: chr8-52233365;