chr8-144514047-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004260.4(RECQL4):āc.1939C>Gā(p.Arg647Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 1,581,154 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R647C) 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.1939C>G | p.Arg647Gly | missense_variant | 12/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1939C>G | p.Arg647Gly | missense_variant | 12/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.868C>G | p.Arg290Gly | missense_variant | 11/20 | 1 | |||
RECQL4 | ENST00000534626.6 | c.310C>G | p.Arg104Gly | missense_variant | 3/8 | 5 | |||
RECQL4 | ENST00000532846.2 | c.796C>G | p.Arg266Gly | missense_variant | 8/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000280 AC: 4AN: 1429058Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 708254
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74292
ClinVar
Submissions by phenotype
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 | Dec 09, 2021 | This sequence change replaces arginine with glycine at codon 647 of the RECQL4 protein (p.Arg647Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (gnomAD no frequency). 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: 459358). 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