rs4539242

chr10-98388301-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032709.3(PYROXD2):c.1447+53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,590,216 control chromosomes in the GnomAD database, including 138,582 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (22409 hom., cov: 30)
  • Exomes 𝑓: 0.39 (116173 hom.)
• Consequence: PYROXD2 NM_032709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.20

Genes affected

PYROXD2 (HGNC:23517): (pyridine nucleotide-disulphide oxidoreductase domain 2) Predicted to enable oxidoreductase activity. Involved in mitochondrion organization. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYROXD2	NM_032709.3	c.1447+53A>G		intron_variant		ENST00000370575.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYROXD2	ENST00000370575.5	c.1447+53A>G		intron_variant		1	NM_032709.3	P1
PYROXD2	ENST00000483923.5	n.2334-994A>G		intron_variant, non_coding_transcript_variant		1
PYROXD2	ENST00000464808.1	n.83+53A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77494 AN: 151626 Hom.: 22352 Cov.: 30

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.389 AC: 558952 AN: 1438472 Hom.: 116173 Cov.: 26 AF XY: 0.391 AC XY: 280001 AN XY: 716520

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.511 AC: 77601 AN: 151744 Hom.: 22409 Cov.: 30 AF XY: 0.518 AC XY: 38440 AN XY: 74154

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.463

Alfa AF: 0.386 Hom.: 11328

Bravo AF: 0.530

Asia WGS AF: 0.565 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.0040
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4539242; hg19: chr10-100148058;