12-21440103-T-C

Position:

• chr12-21440103-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024854.5(PYROXD1):​c.85-265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,940 control chromosomes in the GnomAD database, including 18,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (18612 hom., cov: 32)
• Consequence: PYROXD1 NM_024854.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.639

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-21440103-T-C is Benign according to our data. Variant chr12-21440103-T-C is described in ClinVar as [Benign]. Clinvar id is 1265652.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYROXD1	NM_024854.5	c.85-265T>C		intron_variant		ENST00000240651.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYROXD1	ENST00000240651.14	c.85-265T>C		intron_variant		1	NM_024854.5	P1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75042 AN: 151822 Hom.: 18592 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.510

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.494 AC: 75108 AN: 151940 Hom.: 18612 Cov.: 32 AF XY: 0.492 AC XY: 36579 AN XY: 74276

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.514

Alfa AF: 0.487 Hom.: 2273

Bravo AF: 0.500

Asia WGS AF: 0.553 AC: 1920 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs7298300; hg19: chr12-21593037;