8-51345869-A-T

Variant names:

• chr8-51345869-A-T
• rs11774588
• NM_144651.5:c.3980T>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.3980T>A​(p.Val1327Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,612,452 control chromosomes in the GnomAD database, including 724 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. V1327I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.041 (266 hom., cov: 32)
  • Exomes 𝑓: 0.017 (458 hom.)
• Consequence: PXDNL NM_144651.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.177
• Publications: 6 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004524559).
• BP6: Variant 8-51345869-A-T is Benign according to our data. Variant chr8-51345869-A-T is described in ClinVar as Benign. ClinVar VariationId is 3056506.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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.3980T>A	p.Val1327Asp	missense	Exon 20 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.3980T>A	p.Val1327Asp	missense	Exon 20 of 23	ENSP00000348645.4	A1KZ92-1
	PXDNL	ENST00000894552.1		c.4160T>A	p.Val1387Asp	missense	Exon 21 of 24	ENSP00000564611.1
	PXDNL	ENST00000894549.1		c.3908T>A	p.Val1303Asp	missense	Exon 19 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes AF: 0.0408 AC: 6216 AN: 152194 Hom.: 265 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0289

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0382

GnomAD2 exomes AF: 0.0209 AC: 5210 AN: 248980 AF XY: 0.0202

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.0272

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.000882

Gnomad NFE exome AF: 0.0144

Gnomad OTH exome AF: 0.0200

GnomAD4 exome AF: 0.0170 AC: 24876 AN: 1460140 Hom.: 458 Cov.: 29 AF XY: 0.0173 AC XY: 12536 AN XY: 726482

African (AFR) AF: 0.112 AC: 3757 AN: 33432

American (AMR) AF: 0.0205 AC: 918 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 720 AN: 26124

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39690

South Asian (SAS) AF: 0.0282 AC: 2428 AN: 86218

European-Finnish (FIN) AF: 0.00107 AC: 57 AN: 53390

Middle Eastern (MID) AF: 0.0464 AC: 267 AN: 5758

European-Non Finnish (NFE) AF: 0.0138 AC: 15338 AN: 1110504

Other (OTH) AF: 0.0230 AC: 1388 AN: 60310

GnomAD4 genome AF: 0.0409 AC: 6224 AN: 152312 Hom.: 266 Cov.: 32 AF XY: 0.0396 AC XY: 2948 AN XY: 74494

African (AFR) AF: 0.107 AC: 4463 AN: 41546

American (AMR) AF: 0.0284 AC: 434 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4832

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10630

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 977 AN: 68026

Other (OTH) AF: 0.0378 AC: 80 AN: 2114

Alfa AF: 0.0236 Hom.: 25

Bravo AF: 0.0457

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.0106 AC: 41

ESP6500AA AF: 0.103 AC: 394

ESP6500EA AF: 0.0181 AC: 149

ExAC AF: 0.0219 AC: 2645

Asia WGS AF: 0.0180 AC: 62 AN: 3478

EpiCase AF: 0.0176

EpiControl AF: 0.0183

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	0.042
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.7
DANN	Benign	0.50
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00022	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.18
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.8	N
REVEL	Uncertain	0.30
Sift	Benign	0.58	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.048
MPC		0.18
ClinPred		0.00030	T
GERP RS		0.082
Varity_R		0.062
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs11774588; hg19: chr8-52258429;