rs1554897134
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004260.4(RECQL4):c.2866_2885+19del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L956L) has been classified as Likely benign.
Frequency
Consequence
NM_004260.4 splice_donor, splice_donor_5th_base, coding_sequence, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2866_2885+19del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 16/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2866_2885+19del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 16/21 | 1 | NM_004260.4 | P1 | ||
ENST00000580385.1 | n.68_106del | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247200Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134786
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459606Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 725946
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 459438). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant results in the deletion of part of exon 16 (c.2866_2885+19del) of the RECQL4 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at