NM_002907.4:c.*306A>G

Variant names:

• chr12-21469888-T-C
• rs71582885
• NM_002907.4:c.*306A>G

Variant summary

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

The NM_002907.4(RECQL):​c.*306A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 209,530 control chromosomes in the GnomAD database, including 176 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 (116 hom., cov: 32)
  • Exomes 𝑓: 0.043 (60 hom.)
• Consequence: RECQL NM_002907.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.997
• Publications: 1 publications found

Genes affected

RECQL (HGNC:9948): (RecQ like helicase) The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer. [provided by RefSeq, Jan 2017]

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-21469888-T-C is Benign according to our data. Variant chr12-21469888-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1223508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002907.4. 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
	RECQL	NM_002907.4	MANE Select	c.*306A>G		3_prime_UTR	Exon 15 of 15	NP_002898.2
	PYROXD1	NM_024854.5	MANE Select	c.*1134T>C		3_prime_UTR	Exon 12 of 12	NP_079130.2	Q8WU10-1
	RECQL	NM_032941.3		c.*306A>G		3_prime_UTR	Exon 16 of 16	NP_116559.1	P46063

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	ENST00000444129.7	TSL:2 MANE Select	c.*306A>G		3_prime_UTR	Exon 15 of 15	ENSP00000416739.2	P46063
	PYROXD1	ENST00000240651.14	TSL:1 MANE Select	c.*1134T>C		3_prime_UTR	Exon 12 of 12	ENSP00000240651.9	Q8WU10-1
	RECQL	ENST00000421138.6	TSL:1	c.*306A>G		3_prime_UTR	Exon 16 of 16	ENSP00000395449.2	P46063

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4912 AN: 152010 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.00857

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0433 AC: 2483 AN: 57402 Hom.: 60 Cov.: 0 AF XY: 0.0435 AC XY: 1358 AN XY: 31234

African (AFR) AF: 0.0100 AC: 12 AN: 1198

American (AMR) AF: 0.0364 AC: 114 AN: 3136

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 81 AN: 1524

East Asian (EAS) AF: 0.000456 AC: 1 AN: 2194

South Asian (SAS) AF: 0.0362 AC: 218 AN: 6026

European-Finnish (FIN) AF: 0.0213 AC: 56 AN: 2632

Middle Eastern (MID) AF: 0.106 AC: 23 AN: 216

European-Non Finnish (NFE) AF: 0.0493 AC: 1838 AN: 37314

Other (OTH) AF: 0.0443 AC: 140 AN: 3162

GnomAD4 genome AF: 0.0322 AC: 4906 AN: 152128 Hom.: 116 Cov.: 32 AF XY: 0.0308 AC XY: 2290 AN XY: 74390

African (AFR) AF: 0.00855 AC: 355 AN: 41530

American (AMR) AF: 0.0392 AC: 598 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4826

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0481 AC: 3271 AN: 67954

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0400 Hom.: 27

Bravo AF: 0.0331

Asia WGS AF: 0.0150 AC: 52 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-1.0
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: rs71582885; hg19: chr12-21622822;