Variant 12-21437854-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024854.5(PYROXD1):c.84+40C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,570,224 control chromosomes in the GnomAD database, including 189,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18583 hom., cov: 33)

Exomes 𝑓: 0.49 ( 171057 hom. )

Consequence

PYROXD1
NM_024854.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.302

Variant links:

Genes affected

PYROXD1 (HGNC:26162): (pyridine nucleotide-disulphide oxidoreductase domain 1) This gene encodes a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins that catalyze the pyridine nucleotide-dependent reduction of thiol residues in other proteins. The encoded protein belongs to the class I pyridine nucleotide-disulphide oxidoreductase family but lacks the C-terminal dimerization domain found in other family members and instead has a C-terminal nitrile reductase domain. It localizes to the nucleus and to striated sarcomeric compartments. Naturally occurring mutations in this gene cause early-onset myopathy with internalized nuclei and myofibrillar disorganization. A pseudogene of this gene has been defined on chromosome 11. [provided by RefSeq, Apr 2017]

PYROXD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 12-21437854-C-A is Benign according to our data. Variant chr12-21437854-C-A is described in ClinVar as [Benign]. Clinvar id is 1253388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PYROXD1	NM_024854.5 linkuse as main transcript	c.84+40C>A	intron_variant	ENST00000240651.14
PYROXD1	NM_001350913.2 linkuse as main transcript	c.-620+40C>A	intron_variant
PYROXD1	XM_006719153.4 linkuse as main transcript	c.84+40C>A	intron_variant
PYROXD1	XM_047429554.1 linkuse as main transcript	c.84+40C>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PYROXD1	ENST00000240651.14 linkuse as main transcript	c.84+40C>A	intron_variant	1	NM_024854.5	P1	Q8WU10-1
PYROXD1	ENST00000544970.5 linkuse as main transcript	c.84+40C>A	intron_variant, NMD_transcript_variant	1
PYROXD1	ENST00000375266.8 linkuse as main transcript	c.84+40C>A	intron_variant, NMD_transcript_variant	5
PYROXD1	ENST00000543476.5 linkuse as main transcript	c.84+40C>A	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

75014

AN:

152040

Hom.:

18563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.539

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.510

GnomAD3 exomes

AF:

0.488

AC:

104479

AN:

214048

Hom.:

25398

AF XY:

0.487

AC XY:

56421

AN XY:

115776

show subpopulations

Gnomad AFR exome

AF:

0.496

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.572

Gnomad SAS exome

AF:

0.463

Gnomad FIN exome

AF:

0.448

Gnomad NFE exome

AF:

0.492

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.491

AC:

696339

AN:

1418066

Hom.:

171057

Cov.:

AF XY:

0.489

AC XY:

344841

AN XY:

704620

show subpopulations

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.470

Gnomad4 EAS exome

AF:

0.560

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.446

Gnomad4 NFE exome

AF:

0.493

Gnomad4 OTH exome

AF:

0.505

GnomAD4 genome

AF:

0.493

AC:

75080

AN:

152158

Hom.:

18583

Cov.:

AF XY:

0.492

AC XY:

36568

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.510

Gnomad4 ASJ

AF:

0.462

Gnomad4 EAS

AF:

0.555

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.444

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.515

Alfa

AF:

0.492

Hom.:

11313

Bravo

AF:

0.500

Asia WGS

AF:

0.555

AC:

1931

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Myofibrillar myopathy 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.9

DANN

Benign

0.87

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over