NM_024854.5:c.85-265T>C

Variant names:

• chr12-21440103-T-C
• rs7298300
• NM_024854.5:c.85-265T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• myofibrillar myopathy 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024854.5. 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
	PYROXD1	NM_024854.5	MANE Select	c.85-265T>C		intron	N/A	NP_079130.2	Q8WU10-1
	PYROXD1	NM_001350912.2		c.-129-265T>C		intron	N/A	NP_001337841.1	Q8WU10-2
	PYROXD1	NM_001350913.2		c.-619-265T>C		intron	N/A	NP_001337842.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYROXD1	ENST00000240651.14	TSL:1 MANE Select	c.85-265T>C		intron	N/A	ENSP00000240651.9	Q8WU10-1
	PYROXD1	ENST00000544970.5	TSL:1	n.85-265T>C		intron	N/A	ENSP00000439106.1	B4DEW4
	PYROXD1	ENST00000887643.1		c.85-265T>C		intron	N/A	ENSP00000557702.1

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

African (AFR) AF: 0.504 AC: 20887 AN: 41402

American (AMR) AF: 0.510 AC: 7795 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2862 AN: 5164

South Asian (SAS) AF: 0.448 AC: 2160 AN: 4818

European-Finnish (FIN) AF: 0.445 AC: 4695 AN: 10554

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33356 AN: 67950

Other (OTH) AF: 0.514 AC: 1085 AN: 2110

Alfa AF: 0.488 Hom.: 2372

Bravo AF: 0.500

Asia WGS AF: 0.553 AC: 1920 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.55
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7298300; hg19: chr12-21593037;