rs766038992
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004260.4(RECQL4):c.2894C>T(p.Pro965Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,612,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 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
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000364 AC: 9AN: 247028Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 134844
GnomAD4 exome AF: 0.0000384 AC: 56AN: 1460206Hom.: 0 Cov.: 66 AF XY: 0.0000358 AC XY: 26AN XY: 726352
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 34 AF XY: 0.0000404 AC XY: 3AN XY: 74344
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.2894C>T (p.P965L) alteration is located in exon 17 (coding exon 17) of the RECQL4 gene. This alteration results from a C to T substitution at nucleotide position 2894, causing the proline (P) at amino acid position 965 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Baller-Gerold syndrome Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 965 of the RECQL4 protein (p.Pro965Leu). This variant is present in population databases (rs766038992, 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: 529018). 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