10-98388056-G-T

Variant summary

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

The NM_032709.3(PYROXD2):c.1447+298C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 328,062 control chromosomes in the GnomAD database, including 30,763 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 0.45 (16168 hom., cov: 32)
  • Exomes 𝑓: 0.39 (14595 hom.)
• Consequence: PYROXD2 NM_032709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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 = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYROXD2	NM_032709.3	c.1447+298C>A		intron_variant		ENST00000370575.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYROXD2	ENST00000370575.5	c.1447+298C>A		intron_variant		1	NM_032709.3	P1
PYROXD2	ENST00000483923.5	n.2334-749C>A		intron_variant, non_coding_transcript_variant		1
PYROXD2	ENST00000464808.1	n.112C>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67966 AN: 151872 Hom.: 16138 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.393 AC: 69221 AN: 176072 Hom.: 14595 Cov.: 0 AF XY: 0.404 AC XY: 38110 AN XY: 94316

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.530

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.448 AC: 68046 AN: 151990 Hom.: 16168 Cov.: 32 AF XY: 0.454 AC XY: 33752 AN XY: 74278

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.408

Alfa AF: 0.363 Hom.: 4578

Bravo AF: 0.459

Asia WGS AF: 0.527 AC: 1832 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	4.5
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2147897; hg19: chr10-100147813;