8-51372094-CA-CAAAAA

Variant names:

• chr8-51372094-C-CAAAA
• rs5891410
• NM_144651.5:c.3693-17_3693-14dupTTTT

Variant summary

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

The NM_144651.5(PXDNL):​c.3693-17_3693-14dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000884 in 1,131,776 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PXDNL NM_144651.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.3693-17_3693-14dupTTTT		intron_variant	Intron 18 of 22	ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5	c.3693-17_3693-14dupTTTT		intron_variant	Intron 18 of 22	1	NM_144651.5	ENSP00000348645.4
PXDNL	ENST00000522933.5	c.912-17_912-14dupTTTT		intron_variant	Intron 1 of 5	5		ENSP00000428114.1
PXDNL	ENST00000522628.5	n.1491-17_1491-14dupTTTT		intron_variant	Intron 2 of 4	2		ENSP00000429855.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 148924 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.84e-7 AC: 1 AN: 1131776 Hom.: 0 Cov.: 28 AF XY: 0.00000178 AC XY: 1 AN XY: 560720

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27380

American (AMR) AF: 0.00 AC: 0 AN: 29352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20926

East Asian (EAS) AF: 0.00 AC: 0 AN: 30782

South Asian (SAS) AF: 0.00 AC: 0 AN: 67320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4606

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 861984

Other (OTH) AF: 0.00 AC: 0 AN: 48372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 148924 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72556

African (AFR) AF: 0.00 AC: 0 AN: 40004

American (AMR) AF: 0.00 AC: 0 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 5052

South Asian (SAS) AF: 0.00 AC: 0 AN: 4740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67468

Other (OTH) AF: 0.00 AC: 0 AN: 2042

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5891410; hg19: chr8-52284654;