rs750304658
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004260.4(RECQL4):c.2251C>T(p.Arg751Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000559 in 1,609,550 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. R751Q) 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.2251C>T | p.Arg751Trp | missense_variant | 14/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2251C>T | p.Arg751Trp | missense_variant | 14/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.1180C>T | p.Arg394Trp | missense_variant | 13/20 | 1 | |||
ENST00000580385.1 | n.272-176G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.622C>T | p.Arg208Trp | missense_variant | 5/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000722 AC: 11AN: 152264Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000330 AC: 8AN: 242084Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132826
GnomAD4 exome AF: 0.0000542 AC: 79AN: 1457286Hom.: 0 Cov.: 46 AF XY: 0.0000469 AC XY: 34AN XY: 725150
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74394
ClinVar
Submissions by phenotype
Baller-Gerold syndrome;C1849453:Rapadilino syndrome;C5203410:Rothmund-Thomson syndrome type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 18, 2021 | - - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 751 of the RECQL4 protein (p.Arg751Trp). This variant is present in population databases (rs750304658, 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: 406903). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RECQL4 protein function. 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