12-21470222-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002907.4(RECQL):c.1922C>T(p.Ala641Val) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002907.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RECQL | ENST00000444129.7 | c.1922C>T | p.Ala641Val | missense_variant | Exon 15 of 15 | 2 | NM_002907.4 | ENSP00000416739.2 | ||
RECQL | ENST00000421138.6 | c.1922C>T | p.Ala641Val | missense_variant | Exon 16 of 16 | 1 | ENSP00000395449.2 | |||
PYROXD1 | ENST00000240651.14 | c.*1468G>A | 3_prime_UTR_variant | Exon 12 of 12 | 1 | NM_024854.5 | ENSP00000240651.9 | |||
PYROXD1 | ENST00000538582.5 | c.*1468G>A | 3_prime_UTR_variant | Exon 12 of 12 | 2 | ENSP00000438505.1 |
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2AN: 1458184Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1AN XY: 725250
GnomAD4 genome Cov.: 29
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.A641V variant (also known as c.1922C>T), located in coding exon 14 of the RECQL gene, results from a C to T substitution at nucleotide position 1922. The alanine at codon 641 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 641 of the RECQL protein (p.Ala641Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant has not been reported in the literature in individuals with RECQL-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at