12-21470215-TTTC-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_002907.4(RECQL):​c.1926_1928delGAA​(p.Lys643del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Consequence

RECQL
NM_002907.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_002907.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RECQLNM_002907.4 linkc.1926_1928delGAA p.Lys643del disruptive_inframe_deletion Exon 15 of 15 ENST00000444129.7 NP_002898.2
PYROXD1NM_024854.5 linkc.*1464_*1466delCTT 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 Appris UniProt
RECQLENST00000444129.7 linkc.1926_1928delGAA p.Lys643del disruptive_inframe_deletion Exon 15 of 15 2 NM_002907.4 ENSP00000416739.2 P46063
RECQLENST00000421138.6 linkc.1926_1928delGAA p.Lys643del disruptive_inframe_deletion Exon 16 of 16 1 ENSP00000395449.2 P46063
PYROXD1ENST00000240651.14 linkc.*1464_*1466delCTT 3_prime_UTR_variant Exon 12 of 12 1 NM_024854.5 ENSP00000240651.9 Q8WU10-1
PYROXD1ENST00000538582.5 linkc.*1464_*1466delCTT 3_prime_UTR_variant Exon 12 of 12 2 ENSP00000438505.1 Q8WU10-2

Frequencies

GnomAD3 genomes
Cov.:
29
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
29
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

RECON progeroid syndrome Uncertain:1
Jan 17, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-21623149; API