12-21470188-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002907.4(RECQL):c.*6A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,610,240 control chromosomes in the GnomAD database, including 155,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11199 hom., cov: 30)

Exomes 𝑓: 0.44 ( 144294 hom. )

Consequence

RECQL
NM_002907.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.78

Publications

12 publications found

Variant links:

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]

RECQL links:

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)

PYROXD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-21470188-T-G is Benign according to our data. Variant chr12-21470188-T-G is described in ClinVar as Benign. ClinVar VariationId is 1242890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.487 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RECQL	NM_002907.4	MANE Select	c.*6A>C	3_prime_UTR	Exon 15 of 15	NP_002898.2
PYROXD1	NM_024854.5	MANE Select	c.*1434T>G	3_prime_UTR	Exon 12 of 12	NP_079130.2	Q8WU10-1
RECQL	NM_032941.3		c.*6A>C	3_prime_UTR	Exon 16 of 16	NP_116559.1	P46063

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RECQL	ENST00000444129.7	TSL:2 MANE Select	c.*6A>C	3_prime_UTR	Exon 15 of 15	ENSP00000416739.2	P46063
PYROXD1	ENST00000240651.14	TSL:1 MANE Select	c.*1434T>G	3_prime_UTR	Exon 12 of 12	ENSP00000240651.9	Q8WU10-1
RECQL	ENST00000421138.6	TSL:1	c.*6A>C	3_prime_UTR	Exon 16 of 16	ENSP00000395449.2	P46063

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54483

AN:

151360

Hom.:

11202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.521

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.335

GnomAD2 exomes

AF:

0.431

AC:

107141

AN:

248366

AF XY:

0.436

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.424

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.435

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.440

AC:

642521

AN:

1458762

Hom.:

144294

Cov.:

AF XY:

0.442

AC XY:

321088

AN XY:

725642

show subpopulations

African (AFR)

AF:

0.127

AC:

4246

AN:

33336

American (AMR)

AF:

0.460

AC:

20411

AN:

44414

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

10957

AN:

26014

East Asian (EAS)

AF:

0.438

AC:

17344

AN:

39580

South Asian (SAS)

AF:

0.495

AC:

42564

AN:

85966

European-Finnish (FIN)

AF:

0.518

AC:

27634

AN:

53368

Middle Eastern (MID)

AF:

0.278

AC:

1595

AN:

5734

European-Non Finnish (NFE)

AF:

0.444

AC:

493241

AN:

1110146

Other (OTH)

AF:

0.407

AC:

24529

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

17386

34772

52158

69544

86930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14948

29896

44844

59792

74740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.360

AC:

54480

AN:

151478

Hom.:

11199

Cov.:

AF XY:

0.366

AC XY:

27085

AN XY:

73988

show subpopulations

African (AFR)

AF:

0.145

AC:

5987

AN:

41418

American (AMR)

AF:

0.399

AC:

6053

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1480

AN:

3466

East Asian (EAS)

AF:

0.445

AC:

2289

AN:

5146

South Asian (SAS)

AF:

0.504

AC:

2424

AN:

4808

European-Finnish (FIN)

AF:

0.521

AC:

5420

AN:

10398

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.438

AC:

29707

AN:

67756

Other (OTH)

AF:

0.331

AC:

694

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1610

3220

4829

6439

8049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.404

Hom.:

5493

Bravo

AF:

0.339

Asia WGS

AF:

0.395

AC:

1365

AN:

3466

EpiCase

AF:

0.418

EpiControl

AF:

0.409

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.19

(source)

DANN

Benign

0.55

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over