rs11046048

Variant names:

• chr12-21439266-A-C
• rs11046048
• NM_024854.5:c.85-1102A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-21439266-A-C
• chr12-21439266-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024854.5(PYROXD1):​c.85-1102A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,226 control chromosomes in the GnomAD database, including 1,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1074 hom., cov: 32)
• Consequence: PYROXD1 NM_024854.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 10 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYROXD1	NM_024854.5	c.85-1102A>C		intron_variant	Intron 1 of 11	ENST00000240651.14	NP_079130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYROXD1	ENST00000240651.14	c.85-1102A>C		intron_variant	Intron 1 of 11	1	NM_024854.5	ENSP00000240651.9

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17005 AN: 152106 Hom.: 1073 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0996

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.112 AC: 17028 AN: 152226 Hom.: 1074 Cov.: 32 AF XY: 0.114 AC XY: 8461 AN XY: 74430

African (AFR) AF: 0.126 AC: 5234 AN: 41546

American (AMR) AF: 0.129 AC: 1969 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1591 AN: 5164

South Asian (SAS) AF: 0.103 AC: 495 AN: 4824

European-Finnish (FIN) AF: 0.0996 AC: 1055 AN: 10596

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0868 AC: 5905 AN: 68008

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.0942 Hom.: 2983

Bravo AF: 0.114

Asia WGS AF: 0.188 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.72
PhyloP100		-0.015
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: rs11046048; hg19: chr12-21592200;