rs386833852
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004260.4(RECQL4):c.3072del(p.Val1026CysfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,612,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T1024T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004260.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.3072del | p.Val1026CysfsTer18 | frameshift_variant | 18/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.3072del | p.Val1026CysfsTer18 | frameshift_variant | 18/21 | 1 | NM_004260.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152254Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247120Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134832
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460010Hom.: 0 Cov.: 80 AF XY: 0.0000151 AC XY: 11AN XY: 726274
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152254Hom.: 0 Cov.: 35 AF XY: 0.0000269 AC XY: 2AN XY: 74390
ClinVar
Submissions by phenotype
Rapadilino syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2019 | - - |
Baller-Gerold syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2023 | This sequence change creates a premature translational stop signal (p.Val1026Cysfs*18) in the RECQL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). This variant is present in population databases (rs386833852, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with RAPADILINO syndrome (PMID: 18716613). ClinVar contains an entry for this variant (Variation ID: 56407). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at