10-98390611-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032709.3(PYROXD2):c.1279C>G(p.Leu427Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,443,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: PYROXD2 NM_032709.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10110068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYROXD2	NM_032709.3	c.1279C>G	p.Leu427Val	missense_variant	12/16	ENST00000370575.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYROXD2	ENST00000370575.5	c.1279C>G	p.Leu427Val	missense_variant	12/16	1	NM_032709.3	P1
PYROXD2	ENST00000483923.5	n.2320C>G		non_coding_transcript_exon_variant	12/15	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1443320 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 716256

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000453

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

PYROXD2: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	14
Dann	Benign	0.74
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.084
Sift	Benign	0.51	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.052
MutPred		0.45		Gain of sheet (P = 0.0477);
MVP		0.41
MPC		0.034
ClinPred		0.094	T
GERP RS		2.8
Varity_R		0.039
gMVP		0.24

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-100150368;