ENST00000543476.5:n.-108A>C

Variant names:

• chr12-21437507-G-C
• NM_024854.5:c.-224G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000543476.5(PYROXD1):​n.-224G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PYROXD1 ENST00000543476.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYROXD1	NM_024854.5	c.-224G>C		upstream_gene_variant		ENST00000240651.14	NP_079130.2
PYROXD1	NM_001350913.2	c.-927G>C		upstream_gene_variant			NP_001337842.1
PYROXD1	XM_047429554.1	c.-224G>C		upstream_gene_variant			XP_047285510.1
PYROXD1	XM_006719153.4	c.-224G>C		upstream_gene_variant			XP_006719216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYROXD1	ENST00000240651.14	c.-224G>C		upstream_gene_variant		1	NM_024854.5	ENSP00000240651.9
PYROXD1	ENST00000544970.5	n.-224G>C		upstream_gene_variant		1		ENSP00000439106.1
PYROXD1	ENST00000375266.8	n.-224G>C		upstream_gene_variant		5		ENSP00000364415.4
PYROXD1	ENST00000543476.5	n.-224G>C		upstream_gene_variant		5		ENSP00000440192.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.0
DANN	Benign	0.59

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-21590441;