rs369950284
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_004260.4(RECQL4):c.2069C>T(p.Thr690Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,550,364 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T690S) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2069C>T | p.Thr690Met | missense_variant | 13/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2069C>T | p.Thr690Met | missense_variant | 13/21 | 1 | NM_004260.4 | P1 | |
ENST00000580385.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 151962Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000388 AC: 6AN: 154576Hom.: 0 AF XY: 0.0000610 AC XY: 5AN XY: 81950
GnomAD4 exome AF: 0.0000193 AC: 27AN: 1398286Hom.: 0 Cov.: 47 AF XY: 0.0000246 AC XY: 17AN XY: 689664
GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152078Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74338
ClinVar
Submissions by phenotype
Ovarian cancer Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
Rothmund-Thomson syndrome type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 05, 2022 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 690 of the RECQL4 protein (p.Thr690Met). This variant is present in population databases (rs369950284, gnomAD 0.05%). 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: 528913). 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. 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