chr12-21471035-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002907.4(RECQL):c.1731T>C(p.Asn577Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 1,599,836 control chromosomes in the GnomAD database, including 8,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1074 hom., cov: 32)

Exomes 𝑓: 0.094 ( 7474 hom. )

Consequence

RECQL
NM_002907.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.208

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-21471035-A-G is Benign according to our data. Variant chr12-21471035-A-G is described in ClinVar as [Benign]. Clinvar id is 506623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4 link	c.1731T>C	p.Asn577Asn	synonymous_variant	Exon 14 of 15	ENST00000444129.7	NP_002898.2
PYROXD1	NM_024854.5 link	c.*2281A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000240651.14	NP_079130.2	Q8WU10-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RECQL	ENST00000444129.7 link	c.1731T>C	p.Asn577Asn	synonymous_variant	Exon 14 of 15	2	NM_002907.4	ENSP00000416739.2	P46063
RECQL	ENST00000421138.6 link	c.1731T>C	p.Asn577Asn	synonymous_variant	Exon 15 of 16	1		ENSP00000395449.2	P46063
PYROXD1	ENST00000240651.14 link	c.*2281A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_024854.5	ENSP00000240651.9	Q8WU10-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

16956

AN:

151952

Hom.:

1072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0865

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.108

AC:

25832

AN:

239658

Hom.:

1876

AF XY:

0.107

AC XY:

13894

AN XY:

130206

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0960

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.316

Gnomad SAS exome

AF:

0.0942

Gnomad FIN exome

AF:

0.0982

Gnomad NFE exome

AF:

0.0830

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0943

AC:

136591

AN:

1447766

Hom.:

7474

Cov.:

AF XY:

0.0942

AC XY:

67870

AN XY:

720330

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.0972

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.0846

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.112

AC:

16980

AN:

152070

Hom.:

1074

Cov.:

AF XY:

0.114

AC XY:

8448

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.100

Gnomad4 NFE

AF:

0.0866

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.0950

Hom.:

337

Bravo

AF:

0.114

Asia WGS

AF:

0.182

AC:

634

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 15, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.5

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over