chr8-144514442-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_004260.4(RECQL4):c.1704G>A(p.Lys568Lys) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000683 in 1,611,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004260.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
Publications
- Baller-Gerold syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
- Rothmund-Thomson syndromeInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Rothmund-Thomson syndrome type 2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
- osteosarcomaInheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
- rapadilino syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
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ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 34 show subpopulations
GnomAD2 exomes AF: 0.00000406 AC: 1AN: 246254 AF XY: 0.00000745 show subpopulations
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459146Hom.: 0 Cov.: 36 AF XY: 0.00000827 AC XY: 6AN XY: 725714 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74368 show subpopulations
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
This sequence change affects codon 568 of the RECQL4 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RECQL4 protein. This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individual(s) with Rothmund–Thomson syndrome (PMID: 12734318). This variant is also known as g.3427G>A. ClinVar contains an entry for this variant (Variation ID: 239703). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 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