rs746691436
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004260.4(RECQL4):c.2161C>T(p.Arg721Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000106 in 1,605,844 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R721R) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004260.4 stop_gained
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.2161C>T | p.Arg721Ter | stop_gained | 13/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2161C>T | p.Arg721Ter | stop_gained | 13/21 | 1 | NM_004260.4 | P1 | |
ENST00000580385.1 | n.276G>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000299 AC: 7AN: 234054Hom.: 0 AF XY: 0.0000392 AC XY: 5AN XY: 127588
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1453620Hom.: 0 Cov.: 47 AF XY: 0.00000969 AC XY: 7AN XY: 722446
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Center for Molecular Medicine, Children’s Hospital of Fudan University | Oct 05, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change creates a premature translational stop signal (p.Arg721*) 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 (rs746691436, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Rothmund-Thomson syndrome (PMID: 28486640). ClinVar contains an entry for this variant (Variation ID: 572305). 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