rs781471399
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP3
The NM_004260.4(RECQL4):c.1930_1935delGCCACA(p.Ala644_Thr645del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,583,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004260.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1930_1935delGCCACA | p.Ala644_Thr645del | conservative_inframe_deletion | Exon 12 of 21 | 1 | NM_004260.4 | ENSP00000482313.2 | ||
RECQL4 | ENST00000621189.4 | c.859_864delGCCACA | p.Ala287_Thr288del | conservative_inframe_deletion | Exon 11 of 20 | 1 | ENSP00000483145.1 | |||
RECQL4 | ENST00000534626.6 | c.298_303delGCCACA | p.Ala100_Thr101del | conservative_inframe_deletion | Exon 3 of 8 | 5 | ENSP00000477457.1 | |||
RECQL4 | ENST00000532846.2 | c.784_789delGCCACA | p.Ala262_Thr263del | conservative_inframe_deletion | Exon 8 of 9 | 5 | ENSP00000476551.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152100Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000155 AC: 3AN: 192956Hom.: 0 AF XY: 0.0000190 AC XY: 2AN XY: 105334
GnomAD4 exome AF: 0.0000175 AC: 25AN: 1430902Hom.: 0 AF XY: 0.0000169 AC XY: 12AN XY: 709276
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152100Hom.: 0 Cov.: 34 AF XY: 0.0000404 AC XY: 3AN XY: 74304
ClinVar
Submissions by phenotype
not provided Uncertain:1
In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27247962) -
Baller-Gerold syndrome Uncertain:1
This variant, c.1930_1935del, results in the deletion of 2 amino acid(s) of the RECQL4 protein (p.Ala644_Thr645del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs781471399, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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