12-21470197-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_002907.4(RECQL):​c.1947C>G​(p.Ala649=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 29)

Consequence

RECQL
NM_002907.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.404
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 12-21470197-G-C is Benign according to our data. Variant chr12-21470197-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1996471.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.404 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RECQLNM_002907.4 linkuse as main transcriptc.1947C>G p.Ala649= synonymous_variant 15/15 ENST00000444129.7 NP_002898.2
PYROXD1NM_024854.5 linkuse as main transcriptc.*1443G>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
RECQLENST00000444129.7 linkuse as main transcriptc.1947C>G p.Ala649= synonymous_variant 15/152 NM_002907.4 ENSP00000416739 P1
RECQLENST00000421138.6 linkuse as main transcriptc.1947C>G p.Ala649= synonymous_variant 16/161 ENSP00000395449 P1
PYROXD1ENST00000240651.14 linkuse as main transcriptc.*1443G>C 3_prime_UTR_variant 12/121 NM_024854.5 ENSP00000240651 P1Q8WU10-1
PYROXD1ENST00000538582.5 linkuse as main transcriptc.*1443G>C 3_prime_UTR_variant 12/122 ENSP00000438505 Q8WU10-2

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Cov.:
38
GnomAD4 genome
Cov.:
29

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 27, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
3.0
DANN
Benign
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-21623131; API