10-98384995-G-C

Variant names:

• chr10-98384995-G-C
• rs138840526
• NM_032709.3:c.1627C>G

Variant summary

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

The NM_032709.3(PYROXD2):​c.1627C>G​(p.Arg543Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R543C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PYROXD2 NM_032709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• 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.1627C>G	p.Arg543Gly	missense	Exon 15 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.1627C>G	p.Arg543Gly	missense	Exon 15 of 16	ENSP00000359607.4	Q8N2H3
	PYROXD2	ENST00000483923.5	TSL:1	n.2513C>G		non_coding_transcript_exon	Exon 14 of 15
	PYROXD2	ENST00000906254.1		c.1771C>G	p.Arg591Gly	missense	Exon 15 of 16	ENSP00000576313.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461644 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.2
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.14	B
Vest4		0.71
MutPred		0.55		Loss of solvent accessibility (P = 0.0023)
MVP		0.59
MPC		0.040
ClinPred		0.99	D
GERP RS		2.2
Varity_R		0.49
gMVP		0.78
Mutation Taster		=56/44	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: rs138840526; hg19: chr10-100144752;