rs17620142

Variant names:

• chr12-21440073-G-C
• rs17620142
• NM_024854.5:c.85-295G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-21440073-G-C
• chr12-21440073-G-A
• chr12-21440073-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_024854.5(PYROXD1):​c.85-295G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,142 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.032 (114 hom., cov: 32)
• Consequence: PYROXD1 NM_024854.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.628
• Publications: 0 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=-0.87).
• BP6: Variant 12-21440073-G-C is Benign according to our data. Variant chr12-21440073-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1203918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0321 (4890/152142) while in subpopulation NFE AF = 0.0481 (3273/67996). AF 95% confidence interval is 0.0468. There are 114 homozygotes in GnomAd4. There are 2284 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 114 AR gene

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.85-295G>C		intron	N/A	NP_079130.2	Q8WU10-1
	PYROXD1	NM_001350912.2		c.-129-295G>C		intron	N/A	NP_001337841.1	Q8WU10-2
	PYROXD1	NM_001350913.2		c.-619-295G>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.85-295G>C		intron	N/A	ENSP00000240651.9	Q8WU10-1
	PYROXD1	ENST00000544970.5	TSL:1	n.85-295G>C		intron	N/A	ENSP00000439106.1	B4DEW4
	PYROXD1	ENST00000887643.1		c.85-295G>C		intron	N/A	ENSP00000557702.1

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4896 AN: 152024 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.00841

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0506

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

GnomAD4 genome AF: 0.0321 AC: 4890 AN: 152142 Hom.: 114 Cov.: 32 AF XY: 0.0307 AC XY: 2284 AN XY: 74384

African (AFR) AF: 0.00839 AC: 348 AN: 41496

American (AMR) AF: 0.0393 AC: 601 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0310 AC: 149 AN: 4814

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0481 AC: 3273 AN: 67996

Other (OTH) AF: 0.0510 AC: 108 AN: 2116

Alfa AF: 0.0129 Hom.: 2

Bravo AF: 0.0330

Asia WGS AF: 0.0130 AC: 44 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely 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	-0.87
CADD	Benign	0.47
DANN	Benign	0.78
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism

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: rs17620142; hg19: chr12-21593007;