chr8-51408683-T-C

Position:

• chr8-51408683-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144651.5(PXDNL):​c.2941A>G​(p.Met981Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,595,596 control chromosomes in the GnomAD database, including 556,519 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.82 (51034 hom., cov: 32)
  • Exomes 𝑓: 0.84 (505485 hom.)
• Consequence: PXDNL NM_144651.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0600

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]

PXDNL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0459984E-6).
• BP6: Variant 8-51408683-T-C is Benign according to our data. Variant chr8-51408683-T-C is described in ClinVar as [Benign]. Clinvar id is 403356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.2941A>G	p.Met981Val	missense_variant	17/23	ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5	c.2941A>G	p.Met981Val	missense_variant	17/23	1	NM_144651.5	ENSP00000348645.4
PXDNL	ENST00000522933.5	c.295A>G	p.Met99Val	missense_variant	1/6	5		ENSP00000428114.1
PXDNL	ENST00000522628.5	n.739A>G		non_coding_transcript_exon_variant	1/5	2		ENSP00000429855.1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124263 AN: 151984 Hom.: 50992 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.799

GnomAD3 exomes AF: 0.835 AC: 183493 AN: 219862 Hom.: 76738 AF XY: 0.832 AC XY: 99139 AN XY: 119198

Gnomad AFR exome AF: 0.752

Gnomad AMR exome AF: 0.859

Gnomad ASJ exome AF: 0.805

Gnomad EAS exome AF: 0.932

Gnomad SAS exome AF: 0.811

Gnomad FIN exome AF: 0.839

Gnomad NFE exome AF: 0.831

Gnomad OTH exome AF: 0.828

GnomAD4 exome AF: 0.836 AC: 1207085 AN: 1443494 Hom.: 505485 Cov.: 79 AF XY: 0.835 AC XY: 598087 AN XY: 716516

Gnomad4 AFR exome AF: 0.751

Gnomad4 AMR exome AF: 0.861

Gnomad4 ASJ exome AF: 0.805

Gnomad4 EAS exome AF: 0.935

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.839

Gnomad4 NFE exome AF: 0.838

Gnomad4 OTH exome AF: 0.827

GnomAD4 genome AF: 0.818 AC: 124363 AN: 152102 Hom.: 51034 Cov.: 32 AF XY: 0.819 AC XY: 60902 AN XY: 74354

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.800

Alfa AF: 0.833 Hom.: 64546

Bravo AF: 0.819

TwinsUK AF: 0.847 AC: 3140

ALSPAC AF: 0.840 AC: 3237

ESP6500AA AF: 0.771 AC: 3145

ESP6500EA AF: 0.827 AC: 6937

ExAC AF: 0.819 AC: 98361

Asia WGS AF: 0.862 AC: 2996 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.15
DANN	Benign	0.37
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.7	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.11
Sift	Benign	0.42	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.023
MPC		0.11
ClinPred		0.012	T
GERP RS		-2.8
Varity_R		0.051
gMVP		0.30

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: rs2977020; hg19: chr8-52321243; COSMIC: COSV62494607;