10-98397096-T-C

Variant names:

• chr10-98397096-T-C
• rs7072216
• NM_032709.3:c.625+249A>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.625+249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,064 control chromosomes in the GnomAD database, including 22,300 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 (22300 hom., cov: 32)
• Consequence: PYROXD2 NM_032709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 33 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYROXD2	NM_032709.3	MANE Select	c.625+249A>G		intron	N/A	NP_116098.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYROXD2	ENST00000370575.5	TSL:1 MANE Select	c.625+249A>G		intron	N/A	ENSP00000359607.4
	PYROXD2	ENST00000483923.5	TSL:1	n.1527+249A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77247 AN: 151946 Hom.: 22242 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.509 AC: 77355 AN: 152064 Hom.: 22300 Cov.: 32 AF XY: 0.514 AC XY: 38222 AN XY: 74346

African (AFR) AF: 0.781 AC: 32399 AN: 41488

American (AMR) AF: 0.545 AC: 8329 AN: 15280

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

East Asian (EAS) AF: 0.562 AC: 2904 AN: 5164

South Asian (SAS) AF: 0.536 AC: 2580 AN: 4814

European-Finnish (FIN) AF: 0.403 AC: 4262 AN: 10564

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

European-Non Finnish (NFE) AF: 0.350 AC: 23802 AN: 67970

Other (OTH) AF: 0.465 AC: 979 AN: 2106

Alfa AF: 0.402 Hom.: 31418

Bravo AF: 0.530

Asia WGS AF: 0.568 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.76
PhyloP100		0.066
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: rs7072216; hg19: chr10-100156853; COSMIC: COSV65331105; COSMIC: COSV65331105;