NM_144651.5:c.4137C>T

Variant names:

• chr8-51339633-G-A
• rs138123996
• NM_144651.5:c.4137C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_144651.5(PXDNL):​c.4137C>T​(p.Leu1379Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1379L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PXDNL NM_144651.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.062).
• BP7: Synonymous conserved (PhyloP=0.692 with no splicing effect.

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.4137C>T	p.Leu1379Leu	synonymous	Exon 21 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.4137C>T	p.Leu1379Leu	synonymous	Exon 21 of 23	ENSP00000348645.4	A1KZ92-1
	PXDNL	ENST00000894552.1		c.4317C>T	p.Leu1439Leu	synonymous	Exon 22 of 24	ENSP00000564611.1
	PXDNL	ENST00000894549.1		c.4065C>T	p.Leu1355Leu	synonymous	Exon 20 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000806 AC: 2 AN: 248228 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000583

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: 0.00000137 AC: 2 AN: 1460840 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726634

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.0000449 AC: 2 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 85894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111668

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 12

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.97
DANN	Benign	0.52
PhyloP100		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs138123996; hg19: chr8-52252193;