12-21469812-C-T

Position:

• chr12-21469812-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002907.4(RECQL):​c.*382G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 164,602 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: RECQL NM_002907.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0750

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 12-21469812-C-T is Benign according to our data. Variant chr12-21469812-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1182600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00556 (844/151702) while in subpopulation AFR AF= 0.0157 (649/41334). AF 95% confidence interval is 0.0147. There are 7 homozygotes in gnomad4. There are 414 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.*382G>A		3_prime_UTR_variant	15/15	ENST00000444129.7	NP_002898.2
PYROXD1	NM_024854.5	c.*1058C>T		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.*1058C>T		3_prime_UTR_variant	12/12	1	NM_024854.5	ENSP00000240651	P1
RECQL	ENST00000444129.7	c.*382G>A		3_prime_UTR_variant	15/15	2	NM_002907.4	ENSP00000416739	P1
RECQL	ENST00000421138.6	c.*382G>A		3_prime_UTR_variant	16/16	1		ENSP00000395449	P1
PYROXD1	ENST00000538582.5	c.*1058C>T		3_prime_UTR_variant	12/12	2		ENSP00000438505

Frequencies

GnomAD3 genomes AF: 0.00555 AC: 842 AN: 151582 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00283

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00577

GnomAD4 exome AF: 0.00101 AC: 13 AN: 12900 Hom.: 0 Cov.: 0 AF XY: 0.00112 AC XY: 8 AN XY: 7172

Gnomad4 AFR exome AF: 0.0161

Gnomad4 AMR exome AF: 0.00455

Gnomad4 ASJ exome AF: 0.0410

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000232

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00556 AC: 844 AN: 151702 Hom.: 7 Cov.: 31 AF XY: 0.00558 AC XY: 414 AN XY: 74128

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.00283

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00571

Alfa AF: 0.00451 Hom.: 0

Bravo AF: 0.00603

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.71

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: rs148073000; hg19: chr12-21622746;