chr8-51319989-G-A

Variant names:

• chr8-51319989-G-A
• rs962965318
• NM_144651.5:c.4294C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144651.5(PXDNL):​c.4294C>T​(p.Pro1432Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,416,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PXDNL NM_144651.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.580
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093887895).

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.4294C>T	p.Pro1432Ser	missense	Exon 23 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.4294C>T	p.Pro1432Ser	missense	Exon 23 of 23	ENSP00000348645.4	A1KZ92-1
	PXDNL	ENST00000894552.1		c.4474C>T	p.Pro1492Ser	missense	Exon 24 of 24	ENSP00000564611.1
	PXDNL	ENST00000894549.1		c.4222C>T	p.Pro1408Ser	missense	Exon 22 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000897 AC: 2 AN: 222902 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000739

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1416950 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 704646

African (AFR) AF: 0.00 AC: 0 AN: 31610

American (AMR) AF: 0.0000524 AC: 2 AN: 38186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24772

East Asian (EAS) AF: 0.00 AC: 0 AN: 37584

South Asian (SAS) AF: 0.00 AC: 0 AN: 79016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090118

Other (OTH) AF: 0.00 AC: 0 AN: 58128

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.3
DANN	Benign	0.75
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.58
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.099
Sift	Benign	0.45	T
Sift4G	Benign	0.37	T
Polyphen		0.045	B
Vest4		0.12
MutPred		0.59		Loss of catalytic residue at P1432 (P = 0.0135)
MVP		0.21
MPC		0.15
ClinPred		0.043	T
GERP RS		0.33
Varity_R		0.079
gMVP		0.76
Mutation Taster		=98/2	polymorphism

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: rs962965318; hg19: chr8-52232549;