chr10-98388056-G-T

Variant names:

• chr10-98388056-G-T
• rs2147897
• NM_032709.3:c.1447+298C>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.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
• Publications: 11 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 = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYROXD2	NM_032709.3	c.1447+298C>A		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+298C>A		intron_variant	Intron 13 of 15	1	NM_032709.3	ENSP00000359607.4
PYROXD2	ENST00000483923.5	n.2334-749C>A		intron_variant	Intron 12 of 14	1
PYROXD2	ENST00000464808.1	n.112C>A		non_coding_transcript_exon_variant	Exon 2 of 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

African (AFR) AF: 0.572 AC: 1994 AN: 3484

American (AMR) AF: 0.513 AC: 3247 AN: 6330

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 2090 AN: 4874

East Asian (EAS) AF: 0.500 AC: 3000 AN: 6000

South Asian (SAS) AF: 0.530 AC: 14924 AN: 28162

European-Finnish (FIN) AF: 0.368 AC: 3534 AN: 9606

Middle Eastern (MID) AF: 0.416 AC: 300 AN: 722

European-Non Finnish (NFE) AF: 0.339 AC: 36320 AN: 107136

Other (OTH) AF: 0.391 AC: 3812 AN: 9758

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

African (AFR) AF: 0.596 AC: 24718 AN: 41476

American (AMR) AF: 0.487 AC: 7435 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1604 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2768 AN: 5144

South Asian (SAS) AF: 0.532 AC: 2562 AN: 4818

European-Finnish (FIN) AF: 0.395 AC: 4167 AN: 10542

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23473 AN: 67950

Other (OTH) AF: 0.408 AC: 862 AN: 2112

Alfa AF: 0.366 Hom.: 5258

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
PhyloP100		0.30
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: rs2147897; hg19: chr10-100147813;