rs560476442
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000617875.6(RECQL4):c.3065G>T(p.Arg1022Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,222 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1022H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000617875.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.3065G>T | p.Arg1022Leu | missense_variant | 18/21 | ENST00000617875.6 | NP_004251.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.3065G>T | p.Arg1022Leu | missense_variant | 18/21 | 1 | NM_004260.4 | ENSP00000482313 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152262Hom.: 0 Cov.: 35
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459960Hom.: 0 Cov.: 79 AF XY: 0.00000138 AC XY: 1AN XY: 726236
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152262Hom.: 0 Cov.: 35 AF XY: 0.0000269 AC XY: 2AN XY: 74394
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 27, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RECQL4 protein function. ClinVar contains an entry for this variant (Variation ID: 528947). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1022 of the RECQL4 protein (p.Arg1022Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at