12-21469993-T-C

Position:

• chr12-21469993-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002907.4(RECQL):​c.*201A>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 0.00704 in 660,224 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (96 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (33 hom.)
• Consequence: RECQL NM_002907.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.309

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-21469993-T-C is Benign according to our data. Variant chr12-21469993-T-C is described in ClinVar as [Benign]. Clinvar id is 1237151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.*201A>G		3_prime_UTR_variant	15/15	ENST00000444129.7	NP_002898.2
PYROXD1	NM_024854.5	c.*1239T>C		3_prime_UTR_variant	12/12	ENST00000240651.14	NP_079130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYROXD1	ENST00000240651.14	c.*1239T>C		3_prime_UTR_variant	12/12	1	NM_024854.5	ENSP00000240651	P1
RECQL	ENST00000444129.7	c.*201A>G		3_prime_UTR_variant	15/15	2	NM_002907.4	ENSP00000416739	P1
RECQL	ENST00000421138.6	c.*201A>G		3_prime_UTR_variant	16/16	1		ENSP00000395449	P1
PYROXD1	ENST00000538582.5	c.*1239T>C		3_prime_UTR_variant	12/12	2		ENSP00000438505

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3089 AN: 152026 Hom.: 97 Cov.: 31

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00814

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000530

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.00306 AC: 1555 AN: 508080 Hom.: 33 Cov.: 8 AF XY: 0.00286 AC XY: 734 AN XY: 256864

Gnomad4 AFR exome AF: 0.0690

Gnomad4 AMR exome AF: 0.00704

Gnomad4 ASJ exome AF: 0.0325

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000333

Gnomad4 FIN exome AF: 0.000254

Gnomad4 NFE exome AF: 0.000391

Gnomad4 OTH exome AF: 0.00795

GnomAD4 genome AF: 0.0203 AC: 3093 AN: 152144 Hom.: 96 Cov.: 31 AF XY: 0.0196 AC XY: 1459 AN XY: 74398

Gnomad4 AFR AF: 0.0666

Gnomad4 AMR AF: 0.00812

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000530

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0160 Hom.: 6

Bravo AF: 0.0234

Asia WGS AF: 0.00579 AC: 21 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.66

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

LitVar

Other links and lift over

dbSNP: rs74067191; hg19: chr12-21622927;