8-144514937-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004260.4(RECQL4):āc.1619A>Cā(p.Gln540Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_004260.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1619A>C | p.Gln540Pro | missense_variant, splice_region_variant | 9/21 | 1 | NM_004260.4 | ENSP00000482313.2 | ||
RECQL4 | ENST00000621189.4 | c.548A>C | p.Gln183Pro | missense_variant, splice_region_variant | 8/20 | 1 | ENSP00000483145.1 | |||
RECQL4 | ENST00000532846.2 | c.473A>C | p.Gln158Pro | missense_variant, splice_region_variant | 5/9 | 5 | ENSP00000476551.1 | |||
RECQL4 | ENST00000688394.1 | n.642A>C | splice_region_variant, non_coding_transcript_exon_variant | 3/4 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.00000817 AC: 2AN: 244754Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133588
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458922Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 725694
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2024 | The p.Q540P variant (also known as c.1619A>C), located in coding exon 9 of the RECQL4 gene, results from an A to C substitution at nucleotide position 1619. The glutamine at codon 540 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 31, 2023 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 540 of the RECQL4 protein (p.Gln540Pro). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 459335). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at