12-21470193-A-C

Position:

• chr12-21470193-A-C

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.*1T>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 0.000387 in 1,611,560 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: RECQL NM_002907.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

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=-0.91).
• BP6: Variant 12-21470193-A-C is Benign according to our data. Variant chr12-21470193-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1219632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00209 (317/151998) while in subpopulation AFR AF= 0.00739 (307/41518). AF 95% confidence interval is 0.00671. There are 0 homozygotes in gnomad4. There are 141 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.*1T>G		3_prime_UTR_variant	15/15	ENST00000444129.7	NP_002898.2
PYROXD1	NM_024854.5	c.*1439A>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.*1439A>C		3_prime_UTR_variant	12/12	1	NM_024854.5	ENSP00000240651	P1
RECQL	ENST00000444129.7	c.*1T>G		3_prime_UTR_variant	15/15	2	NM_002907.4	ENSP00000416739	P1
RECQL	ENST00000421138.6	c.*1T>G		3_prime_UTR_variant	16/16	1		ENSP00000395449	P1
PYROXD1	ENST00000538582.5	c.*1439A>C		3_prime_UTR_variant	12/12	2		ENSP00000438505

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 317 AN: 151880 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00742

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000591

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.000429 AC: 105 AN: 245028 Hom.: 1 AF XY: 0.000264 AC XY: 35 AN XY: 132750

Gnomad AFR exome AF: 0.00562

Gnomad AMR exome AF: 0.000456

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000210 AC: 307 AN: 1459562 Hom.: 2 Cov.: 38 AF XY: 0.000169 AC XY: 123 AN XY: 726074

Gnomad4 AFR exome AF: 0.00714

Gnomad4 AMR exome AF: 0.000494

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.000515

GnomAD4 genome AF: 0.00209 AC: 317 AN: 151998 Hom.: 0 Cov.: 29 AF XY: 0.00190 AC XY: 141 AN XY: 74328

Gnomad4 AFR AF: 0.00739

Gnomad4 AMR AF: 0.000590

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000477

Alfa AF: 0.000519 Hom.: 1

Bravo AF: 0.00237

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

Jul 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.51

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: rs143505576; hg19: chr12-21623127;