rs757540549
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004260.4(RECQL4):c.2542C>T(p.Arg848Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,580,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R848H) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2542C>T | p.Arg848Cys | missense_variant | 15/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2542C>T | p.Arg848Cys | missense_variant | 15/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.1471C>T | p.Arg491Cys | missense_variant | 14/20 | 1 | |||
ENST00000580385.1 | n.271+223G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.715C>T | p.Arg239Cys | missense_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000402 AC: 8AN: 199186Hom.: 0 AF XY: 0.0000461 AC XY: 5AN XY: 108464
GnomAD4 exome AF: 0.0000364 AC: 52AN: 1428148Hom.: 0 Cov.: 66 AF XY: 0.0000212 AC XY: 15AN XY: 707458
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 19, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 848 of the RECQL4 protein (p.Arg848Cys). This variant is present in population databases (rs757540549, gnomAD 0.01%). 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: 459411). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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