rs2110165

Variant names:

• chr12-21437854-C-A
• rs2110165
• NM_024854.5:c.84+40C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-21437854-C-A
• chr12-21437854-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024854.5(PYROXD1):​c.84+40C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,570,224 control chromosomes in the GnomAD database, including 189,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18583 hom., cov: 33)
  • Exomes 𝑓: 0.49 (171057 hom.)
• Consequence: PYROXD1 NM_024854.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.302
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 12-21437854-C-A is Benign according to our data. Variant chr12-21437854-C-A is described in ClinVar as Benign. ClinVar VariationId is 1253388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYROXD1	NM_024854.5	c.84+40C>A		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.84+40C>A		intron_variant	Intron 1 of 11	1	NM_024854.5	ENSP00000240651.9

Frequencies

GnomAD3 genomes AF: 0.493 AC: 75014 AN: 152040 Hom.: 18563 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.510

GnomAD2 exomes AF: 0.488 AC: 104479 AN: 214048 AF XY: 0.487

Gnomad AFR exome AF: 0.496

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.470

Gnomad EAS exome AF: 0.572

Gnomad FIN exome AF: 0.448

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.500

GnomAD4 exome AF: 0.491 AC: 696339 AN: 1418066 Hom.: 171057 Cov.: 24 AF XY: 0.489 AC XY: 344841 AN XY: 704620

African (AFR) AF: 0.501 AC: 16444 AN: 32792

American (AMR) AF: 0.480 AC: 19746 AN: 41114

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 11861 AN: 25236

East Asian (EAS) AF: 0.560 AC: 21732 AN: 38822

South Asian (SAS) AF: 0.459 AC: 37943 AN: 82674

European-Finnish (FIN) AF: 0.446 AC: 22863 AN: 51272

Middle Eastern (MID) AF: 0.556 AC: 3152 AN: 5672

European-Non Finnish (NFE) AF: 0.493 AC: 532890 AN: 1081658

Other (OTH) AF: 0.505 AC: 29708 AN: 58826

GnomAD4 genome AF: 0.493 AC: 75080 AN: 152158 Hom.: 18583 Cov.: 33 AF XY: 0.492 AC XY: 36568 AN XY: 74392

African (AFR) AF: 0.501 AC: 20813 AN: 41516

American (AMR) AF: 0.510 AC: 7803 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1604 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2869 AN: 5172

South Asian (SAS) AF: 0.449 AC: 2167 AN: 4830

European-Finnish (FIN) AF: 0.444 AC: 4707 AN: 10592

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

European-Non Finnish (NFE) AF: 0.491 AC: 33365 AN: 67958

Other (OTH) AF: 0.515 AC: 1087 AN: 2112

Alfa AF: 0.492 Hom.: 12911

Bravo AF: 0.500

Asia WGS AF: 0.555 AC: 1931 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Myofibrillar myopathy 8 Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.9
DANN	Benign	0.87
PhyloP100		0.30
PromoterAI		-0.036	Neutral
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: rs2110165; hg19: chr12-21590788;