dbSNP rs2296441: PYROXD2:p.Ala533Pro (chr10-98385025-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032709.3(PYROXD2):c.1597G>C(p.Ala533Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PYROXD2
NM_032709.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.990

Publications

41 publications found

Variant links:

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]

PYROXD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYROXD2	NM_032709.3 link	c.1597G>C	p.Ala533Pro	missense_variant	Exon 15 of 16	ENST00000370575.5	NP_116098.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYROXD2	ENST00000370575.5 link	c.1597G>C	p.Ala533Pro	missense_variant	Exon 15 of 16	1	NM_032709.3	ENSP00000359607.4
PYROXD2	ENST00000483923.5 link	n.2483G>C		non_coding_transcript_exon_variant	Exon 14 of 15	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151866

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74168

African (AFR)

AF:

0.00

AC:

AN:

41336

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67954

Other (OTH)

AF:

0.00

AC:

AN:

2088

Alfa

AF:

0.00

Hom.:

26916

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.7

PhyloP100

0.99

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.27

Sift

Benign

0.25

Sift4G

Benign

0.24

Polyphen

0.93

Vest4

0.52

MutPred

0.64

Loss of loop (P = 0.0203);

MVP

0.56

MPC

0.041

ClinPred

0.96

GERP RS

5.2

Varity_R

0.39

gMVP

0.68

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over