chr8-51408683-T-C

Variant names:

• chr8-51408683-T-C
• rs2977020
• NM_144651.5:c.2941A>G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 23 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 -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 rank	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.2941A>G	p.Met981Val	missense_variant	Exon 17 of 23	ENST00000356297.5	NP_653252.4

Ensembl

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

GnomAD2 exomes AF: 0.835 AC: 183493 AN: 219862 AF XY: 0.832

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 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

African (AFR) AF: 0.751 AC: 24870 AN: 33136

American (AMR) AF: 0.861 AC: 36235 AN: 42088

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 20683 AN: 25692

East Asian (EAS) AF: 0.935 AC: 36222 AN: 38726

South Asian (SAS) AF: 0.808 AC: 67761 AN: 83872

European-Finnish (FIN) AF: 0.839 AC: 43440 AN: 51756

Middle Eastern (MID) AF: 0.766 AC: 4404 AN: 5748

European-Non Finnish (NFE) AF: 0.838 AC: 924122 AN: 1102826

Other (OTH) AF: 0.827 AC: 49348 AN: 59650

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

African (AFR) AF: 0.760 AC: 31558 AN: 41520

American (AMR) AF: 0.852 AC: 13041 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2798 AN: 3464

East Asian (EAS) AF: 0.941 AC: 4819 AN: 5120

South Asian (SAS) AF: 0.804 AC: 3865 AN: 4806

European-Finnish (FIN) AF: 0.831 AC: 8804 AN: 10594

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56733 AN: 67982

Other (OTH) AF: 0.800 AC: 1692 AN: 2114

Alfa AF: 0.831 Hom.: 93702

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
PhyloP100		0.060
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
PromoterAI		-0.038	Neutral
Varity_R		0.051
gMVP		0.30
Mutation Taster		=99/1	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: rs2977020; hg19: chr8-52321243; COSMIC: COSV62494607;