rs780282337
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004260.4(RECQL4):āc.2032G>Cā(p.Val678Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000192 in 1,559,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V678M) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2032G>C | p.Val678Leu | missense_variant | 12/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2032G>C | p.Val678Leu | missense_variant | 12/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.961G>C | p.Val321Leu | missense_variant | 11/20 | 1 | |||
RECQL4 | ENST00000534626.6 | c.403G>C | p.Val135Leu | missense_variant | 3/8 | 5 | |||
RECQL4 | ENST00000532846.2 | c.889G>C | p.Val297Leu | missense_variant | 8/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152018Hom.: 0 Cov.: 34
GnomAD4 exome AF: 7.10e-7 AC: 1AN: 1407720Hom.: 0 Cov.: 36 AF XY: 0.00000144 AC XY: 1AN XY: 695562
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152018Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74248
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 09, 2023 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 678 of the RECQL4 protein (p.Val678Leu). This variant is not present in population databases (gnomAD no frequency). 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: 1411497). 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 expected to disrupt RECQL4 protein function with a positive 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