chr8-51320848-C-T

Variant names:

• chr8-51320848-C-T
• rs7827446
• NM_144651.5:c.4196G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_144651.5(PXDNL):​c.4196G>A​(p.Arg1399Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,612,848 control chromosomes in the GnomAD database, including 63,624 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1399S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.34 (10404 hom., cov: 33)
  • Exomes 𝑓: 0.26 (53220 hom.)
• Consequence: PXDNL NM_144651.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.106
• Publications: 20 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.408999E-5).
• BP6: Variant 8-51320848-C-T is Benign according to our data. Variant chr8-51320848-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060925.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

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.4196G>A	p.Arg1399Lys	missense	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.4196G>A	p.Arg1399Lys	missense	Exon 22 of 23	ENSP00000348645.4	A1KZ92-1
	PXDNL	ENST00000894552.1		c.4376G>A	p.Arg1459Lys	missense	Exon 23 of 24	ENSP00000564611.1
	PXDNL	ENST00000894549.1		c.4124G>A	p.Arg1375Lys	missense	Exon 21 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51532 AN: 151942 Hom.: 10384 Cov.: 33

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.261 AC: 64686 AN: 248124 AF XY: 0.257

Gnomad AFR exome AF: 0.576

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.152

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.264 AC: 384999 AN: 1460788 Hom.: 53220 Cov.: 33 AF XY: 0.262 AC XY: 190398 AN XY: 726728

African (AFR) AF: 0.577 AC: 19282 AN: 33442

American (AMR) AF: 0.222 AC: 9907 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 7544 AN: 26106

East Asian (EAS) AF: 0.142 AC: 5630 AN: 39674

South Asian (SAS) AF: 0.229 AC: 19711 AN: 86210

European-Finnish (FIN) AF: 0.233 AC: 12434 AN: 53368

Middle Eastern (MID) AF: 0.286 AC: 1647 AN: 5762

European-Non Finnish (NFE) AF: 0.263 AC: 292208 AN: 1111202

Other (OTH) AF: 0.276 AC: 16636 AN: 60346

GnomAD4 genome AF: 0.339 AC: 51598 AN: 152060 Hom.: 10404 Cov.: 33 AF XY: 0.332 AC XY: 24666 AN XY: 74326

African (AFR) AF: 0.565 AC: 23438 AN: 41452

American (AMR) AF: 0.250 AC: 3818 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3470

East Asian (EAS) AF: 0.155 AC: 802 AN: 5168

South Asian (SAS) AF: 0.228 AC: 1099 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2446 AN: 10570

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18063 AN: 67988

Other (OTH) AF: 0.327 AC: 688 AN: 2106

Alfa AF: 0.287 Hom.: 31208

Bravo AF: 0.350

TwinsUK AF: 0.277 AC: 1028

ALSPAC AF: 0.254 AC: 978

ESP6500AA AF: 0.540 AC: 2105

ESP6500EA AF: 0.262 AC: 2170

ExAC AF: 0.270 AC: 32625

Asia WGS AF: 0.240 AC: 839 AN: 3478

EpiCase AF: 0.265

EpiControl AF: 0.261

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
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.2
DANN	Benign	0.63
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.078	T
MetaRNN	Benign	0.000074	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.11
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.050
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.019
MPC		0.11
ClinPred		0.00030	T
GERP RS		0.65
Varity_R		0.046
gMVP		0.50
Mutation Taster		=100/0	polymorphism (auto)

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: rs7827446; hg19: chr8-52233408; COSMIC: COSV62478082;