chr10-98384971-G-C

Variant names:

• chr10-98384971-G-C
• rs1190156655
• NM_032709.3:c.1651C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032709.3(PYROXD2):​c.1651C>G​(p.Leu551Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. L551I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PYROXD2 NM_032709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

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.1651C>G	p.Leu551Val	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.1651C>G	p.Leu551Val	missense	Exon 15 of 16	ENSP00000359607.4	Q8N2H3
	PYROXD2	ENST00000483923.5	TSL:1	n.2537C>G		non_coding_transcript_exon	Exon 14 of 15
	PYROXD2	ENST00000906254.1		c.1795C>G	p.Leu599Val	missense	Exon 15 of 16	ENSP00000576313.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.71
MutPred		0.78		Loss of sheet (P = 0.0315)
MVP		0.83
MPC		0.16
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.38
gMVP		0.58
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1190156655; hg19: chr10-100144728;