10-98399379-A-T

Variant names:

• chr10-98399379-A-T
• rs4488133
• NM_032709.3:c.471+723T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032709.3(PYROXD2):​c.471+723T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,150 control chromosomes in the GnomAD database, including 22,264 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 (22264 hom., cov: 32)
• Consequence: PYROXD2 NM_032709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 29 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=-1.0).
• 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.471+723T>A		intron_variant	Intron 5 of 15	ENST00000370575.5	NP_116098.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYROXD2	ENST00000370575.5	c.471+723T>A		intron_variant	Intron 5 of 15	1	NM_032709.3	ENSP00000359607.4
PYROXD2	ENST00000483923.5	n.1373+723T>A		intron_variant	Intron 5 of 14	1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77185 AN: 152032 Hom.: 22207 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.467

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77292 AN: 152150 Hom.: 22264 Cov.: 32 AF XY: 0.513 AC XY: 38161 AN XY: 74374

African (AFR) AF: 0.781 AC: 32423 AN: 41532

American (AMR) AF: 0.545 AC: 8338 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3472

East Asian (EAS) AF: 0.560 AC: 2896 AN: 5168

South Asian (SAS) AF: 0.535 AC: 2581 AN: 4820

European-Finnish (FIN) AF: 0.395 AC: 4182 AN: 10574

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

European-Non Finnish (NFE) AF: 0.350 AC: 23799 AN: 67988

Other (OTH) AF: 0.463 AC: 975 AN: 2104

Alfa AF: 0.433 Hom.: 1951

Bravo AF: 0.530

Asia WGS AF: 0.560 AC: 1946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.029
DANN	Benign	0.32
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4488133; hg19: chr10-100159136;