rs756069461
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004260.4(RECQL4):c.361C>G(p.Pro121Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,521,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000117 AC: 2AN: 171490Hom.: 0 AF XY: 0.0000109 AC XY: 1AN XY: 91416
GnomAD4 exome AF: 0.0000117 AC: 16AN: 1368808Hom.: 0 Cov.: 35 AF XY: 0.00000893 AC XY: 6AN XY: 671646
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function -
Baller-Gerold syndrome Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 121 of the RECQL4 protein (p.Pro121Ala). This variant is present in population databases (rs756069461, gnomAD 0.002%). 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: 528918). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RECQL4 protein function with a negative predictive value of 80%. 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