rs549632316

Variant names:

• chr10-98388470-G-C
• rs549632316
• NM_032709.3:c.1331C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032709.3(PYROXD2):​c.1331C>G​(p.Pro444Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P444S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PYROXD2 NM_032709.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.61
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYROXD2	NM_032709.3	MANE Select	c.1331C>G	p.Pro444Arg	missense	Exon 13 of 16	NP_116098.2	Q8N2H3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYROXD2	ENST00000370575.5	TSL:1 MANE Select	c.1331C>G	p.Pro444Arg	missense	Exon 13 of 16	ENSP00000359607.4	Q8N2H3
	PYROXD2	ENST00000483923.5	TSL:1	n.2334-1163C>G		intron	N/A
	PYROXD2	ENST00000906254.1		c.1475C>G	p.Pro492Arg	missense	Exon 13 of 16	ENSP00000576313.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151508 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000242 AC: 6 AN: 247768 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460566 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726434

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.000157 AC: 7 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 85868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111510

Other (OTH) AF: 0.0000166 AC: 1 AN: 60336

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151626 Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1 AN XY: 74092

African (AFR) AF: 0.00 AC: 0 AN: 41266

American (AMR) AF: 0.000131 AC: 2 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67916

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000113 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.049	T
Eigen	Benign	0.037
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		9.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.26
Sift	Benign	0.15	T
Sift4G	Benign	0.19	T
Polyphen		0.24	B
Vest4		0.71
MutPred		0.62		Loss of glycosylation at T445 (P = 0.0211)
MVP		0.70
MPC		0.038
ClinPred		0.28	T
GERP RS		4.0
Varity_R		0.62
gMVP		0.49
Mutation Taster		=54/46	polymorphism

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: rs549632316; hg19: chr10-100148227;