rs4539242

Variant names:

• chr10-98388301-T-C
• rs4539242
• NM_032709.3:c.1447+53A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 40 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PYROXD2	NM_032709.3	c.1447+53A>G		intron_variant	Intron 13 of 15	ENST00000370575.5	NP_116098.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYROXD2	ENST00000370575.5	c.1447+53A>G		intron_variant	Intron 13 of 15	1	NM_032709.3	ENSP00000359607.4
PYROXD2	ENST00000483923.5	n.2334-994A>G		intron_variant	Intron 12 of 14	1
PYROXD2	ENST00000464808.1	n.83+53A>G		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.796 AC: 26284 AN: 33032

American (AMR) AF: 0.617 AC: 27280 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 11965 AN: 25912

East Asian (EAS) AF: 0.534 AC: 21108 AN: 39518

South Asian (SAS) AF: 0.526 AC: 44675 AN: 84962

European-Finnish (FIN) AF: 0.426 AC: 22186 AN: 52072

Middle Eastern (MID) AF: 0.463 AC: 2596 AN: 5610

European-Non Finnish (NFE) AF: 0.345 AC: 377348 AN: 1093548

Other (OTH) AF: 0.428 AC: 25510 AN: 59582

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

African (AFR) AF: 0.782 AC: 32311 AN: 41344

American (AMR) AF: 0.543 AC: 8278 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1646 AN: 3470

East Asian (EAS) AF: 0.557 AC: 2862 AN: 5136

South Asian (SAS) AF: 0.536 AC: 2565 AN: 4786

European-Finnish (FIN) AF: 0.442 AC: 4650 AN: 10526

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23837 AN: 67930

Other (OTH) AF: 0.463 AC: 976 AN: 2106

Alfa AF: 0.402 Hom.: 32753

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
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4539242; hg19: chr10-100148058;