10-98387303-A-G

Position:

• chr10-98387303-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032709.3(PYROXD2):​c.1452T>C​(p.Phe484=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,610,036 control chromosomes in the GnomAD database, including 123,983 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 (16166 hom., cov: 32)
  • Exomes 𝑓: 0.38 (107817 hom.)
• Consequence: PYROXD2 NM_032709.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.184 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYROXD2	NM_032709.3	c.1452T>C	p.Phe484=	synonymous_variant	14/16	ENST00000370575.5	NP_116098.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYROXD2	ENST00000370575.5	c.1452T>C	p.Phe484=	synonymous_variant	14/16	1	NM_032709.3	ENSP00000359607	P1
PYROXD2	ENST00000483923.5	n.2338T>C		non_coding_transcript_exon_variant	13/15	1
PYROXD2	ENST00000464808.1	n.308T>C		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67969 AN: 151972 Hom.: 16136 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.412

GnomAD3 exomes AF: 0.441 AC: 110455 AN: 250580 Hom.: 25672 AF XY: 0.434 AC XY: 58713 AN XY: 135404

Gnomad AFR exome AF: 0.595

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.538

Gnomad SAS exome AF: 0.519

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.375 AC: 547369 AN: 1457946 Hom.: 107817 Cov.: 31 AF XY: 0.379 AC XY: 274635 AN XY: 725470

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.522

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.447 AC: 68048 AN: 152090 Hom.: 16166 Cov.: 32 AF XY: 0.454 AC XY: 33744 AN XY: 74334

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.408

Alfa AF: 0.368 Hom.: 20069

Bravo AF: 0.459

Asia WGS AF: 0.528 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.45
DANN	Benign	0.61

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: rs4345897; hg19: chr10-100147060; COSMIC: COSV65329765;