rs775200679
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004260.4(RECQL4):c.1460G>A(p.Arg487His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000594 in 1,565,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R487C) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.1460G>A | p.Arg487His | missense_variant | 8/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1460G>A | p.Arg487His | missense_variant | 8/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.389G>A | p.Arg130His | missense_variant | 7/20 | 1 | |||
RECQL4 | ENST00000532846.2 | c.347G>A | p.Arg116His | missense_variant | 4/9 | 5 | |||
RECQL4 | ENST00000688394.1 | n.483G>A | non_coding_transcript_exon_variant | 2/4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000575 AC: 10AN: 173814Hom.: 0 AF XY: 0.0000537 AC XY: 5AN XY: 93180
GnomAD4 exome AF: 0.0000630 AC: 89AN: 1412958Hom.: 0 Cov.: 33 AF XY: 0.0000659 AC XY: 46AN XY: 698498
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2023 | The c.1460G>A (p.R487H) alteration is located in exon 8 (coding exon 8) of the RECQL4 gene. This alteration results from a G to A substitution at nucleotide position 1460, causing the arginine (R) at amino acid position 487 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Rothmund-Thomson syndrome;C0265308:Baller-Gerold syndrome;C1849453:Rapadilino syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 487 of the RECQL4 protein (p.Arg487His). This variant is present in population databases (rs775200679, gnomAD 0.009%). 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: 407015). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RECQL4 protein function with a negative predictive value of 80%. 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