rs760748569
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004260.4(RECQL4):c.2203C>T(p.Arg735Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,609,734 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. R735H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense, splice_region
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.2203C>T | p.Arg735Cys | missense_variant, splice_region_variant | 14/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2203C>T | p.Arg735Cys | missense_variant, splice_region_variant | 14/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.1132C>T | p.Arg378Cys | missense_variant, splice_region_variant | 13/20 | 1 | |||
ENST00000580385.1 | n.272-128G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.574C>T | p.Arg192Cys | missense_variant, splice_region_variant | 5/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000164 AC: 4AN: 243592Hom.: 0 AF XY: 0.0000225 AC XY: 3AN XY: 133440
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1457486Hom.: 0 Cov.: 47 AF XY: 0.00000965 AC XY: 7AN XY: 725204
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74388
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2023 | The c.2203C>T (p.R735C) alteration is located in exon 14 (coding exon 14) of the RECQL4 gene. This alteration results from a C to T substitution at nucleotide position 2203, causing the arginine (R) at amino acid position 735 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 735 of the RECQL4 protein (p.Arg735Cys). This variant is present in population databases (rs760748569, gnomAD 0.02%). 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: 528942). 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. 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