chr8-51339633-G-T

Variant names:

• chr8-51339633-G-T
• rs138123996
• NM_144651.5:c.4137C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_144651.5(PXDNL):​c.4137C>A​(p.Leu1379Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,180 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0022 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (46 hom.)
• Consequence: PXDNL NM_144651.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.692
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-51339633-G-T is Benign according to our data. Variant chr8-51339633-G-T is described in ClinVar as Benign. ClinVar VariationId is 3035044.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.692 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00221 (336/152344) while in subpopulation EAS AF = 0.0499 (259/5192). AF 95% confidence interval is 0.0449. There are 13 homozygotes in GnomAd4. There are 191 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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.4137C>A	p.Leu1379Leu	synonymous	Exon 21 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.4137C>A	p.Leu1379Leu	synonymous	Exon 21 of 23	ENSP00000348645.4	A1KZ92-1
	PXDNL	ENST00000894552.1		c.4317C>A	p.Leu1439Leu	synonymous	Exon 22 of 24	ENSP00000564611.1
	PXDNL	ENST00000894549.1		c.4065C>A	p.Leu1355Leu	synonymous	Exon 20 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 331 AN: 152226 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0498

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00440 AC: 1093 AN: 248228 AF XY: 0.00411

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0562

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00132 AC: 1922 AN: 1460836 Hom.: 46 Cov.: 32 AF XY: 0.00136 AC XY: 991 AN XY: 726634

African (AFR) AF: 0.000239 AC: 8 AN: 33446

American (AMR) AF: 0.0000673 AC: 3 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0357 AC: 1415 AN: 39650

South Asian (SAS) AF: 0.00253 AC: 217 AN: 85894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

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

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111668

Other (OTH) AF: 0.00413 AC: 249 AN: 60344

GnomAD4 genome AF: 0.00221 AC: 336 AN: 152344 Hom.: 13 Cov.: 33 AF XY: 0.00256 AC XY: 191 AN XY: 74502

African (AFR) AF: 0.000433 AC: 18 AN: 41572

American (AMR) AF: 0.00111 AC: 17 AN: 15300

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

East Asian (EAS) AF: 0.0499 AC: 259 AN: 5192

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00108 Hom.: 12

Bravo AF: 0.00243

Asia WGS AF: 0.0300 AC: 105 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PXDNL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.74
DANN	Benign	0.52
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138123996; hg19: chr8-52252193; COSMIC: COSV62488472;