chr12-21437676-CCA-C

Position:

• chr12-21437676-CCA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_024854.5(PYROXD1):​c.-54_-53del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,550,036 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (19 hom.)
• Consequence: PYROXD1 NM_024854.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.38

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 -10 ACMG points.

• BP6: Variant 12-21437676-CCA-C is Benign according to our data. Variant chr12-21437676-CCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1301018.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00791 (1205/152258) while in subpopulation AFR AF= 0.0239 (992/41540). AF 95% confidence interval is 0.0226. There are 17 homozygotes in gnomad4. There are 595 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYROXD1	NM_024854.5	c.-54_-53del		5_prime_UTR_variant	1/12	ENST00000240651.14
PYROXD1	NM_001350913.2	c.-757_-756del		5_prime_UTR_variant	1/11
PYROXD1	XM_006719153.4	c.-54_-53del		5_prime_UTR_variant	1/8
PYROXD1	XM_047429554.1	c.-54_-53del		5_prime_UTR_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYROXD1	ENST00000240651.14	c.-54_-53del		5_prime_UTR_variant	1/12	1	NM_024854.5	P1
PYROXD1	ENST00000375266.8	c.-54_-53del		5_prime_UTR_variant, NMD_transcript_variant	1/13	5
PYROXD1	ENST00000543476.5	c.-54_-53del		5_prime_UTR_variant, NMD_transcript_variant	1/9	5
PYROXD1	ENST00000544970.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00791 AC: 1203 AN: 152140 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00765

GnomAD4 exome AF: 0.00158 AC: 2206 AN: 1397778 Hom.: 19 AF XY: 0.00146 AC XY: 1015 AN XY: 692898

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.00287

Gnomad4 ASJ exome AF: 0.0328

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000149

Gnomad4 FIN exome AF: 0.000178

Gnomad4 NFE exome AF: 0.000234

Gnomad4 OTH exome AF: 0.00430

GnomAD4 genome AF: 0.00791 AC: 1205 AN: 152258 Hom.: 17 Cov.: 32 AF XY: 0.00799 AC XY: 595 AN XY: 74450

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00705 Hom.: 1

Bravo AF: 0.00913

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138292380; hg19: chr12-21590610;