chr8-144514332-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004260.4(RECQL4):c.1735C>G(p.Leu579Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000056 in 1,607,652 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L579M) has been classified 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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.1735C>G | p.Leu579Val | missense_variant | 11/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1735C>G | p.Leu579Val | missense_variant | 11/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.664C>G | p.Leu222Val | missense_variant | 10/20 | 1 | |||
RECQL4 | ENST00000534626.6 | c.106C>G | p.Leu36Val | missense_variant | 2/8 | 5 | |||
RECQL4 | ENST00000532846.2 | c.592C>G | p.Leu198Val | missense_variant | 7/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000165 AC: 4AN: 243152Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132726
GnomAD4 exome AF: 0.00000412 AC: 6AN: 1455352Hom.: 0 Cov.: 36 AF XY: 0.00000415 AC XY: 3AN XY: 723458
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152300Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74472
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 22, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 579 of the RECQL4 protein (p.Leu579Val). This variant is present in population databases (rs552226907, gnomAD 0.02%). 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: 574626). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RECQL4 protein function. 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