rs765804620
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_004260.4(RECQL4):c.3541C>T(p.Arg1181Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,612,426 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 (★). Synonymous variant affecting the same amino acid position (i.e. R1181R) has been classified as Likely benign.
Frequency
Consequence
NM_004260.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.3541C>T | p.Arg1181Ter | stop_gained | 21/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.3541C>T | p.Arg1181Ter | stop_gained | 21/21 | 1 | NM_004260.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 247404Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134886
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460248Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 726394
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | This sequence change creates a premature translational stop signal (p.Arg1181*) in the RECQL4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 28 amino acid(s) of the RECQL4 protein. This variant is present in population databases (rs765804620, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with lower grade glioma (PMID: 29625052). ClinVar contains an entry for this variant (Variation ID: 406948). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the C-terminus of the RECQL4 protein. Other variant(s) that disrupt this region (p.Thr1200ArgfsX26 ) have been observed in individuals with RECQL4-related conditions (PMID: 18716613). This suggests that this may be a clinically significant region of the protein. 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