8-144513295-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004260.4(RECQL4):c.2386G>A(p.Glu796Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000431 in 1,599,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. E796D) 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.2386G>A | p.Glu796Lys | missense_variant | 14/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2386G>A | p.Glu796Lys | missense_variant | 14/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.1315G>A | p.Glu439Lys | missense_variant | 13/20 | 1 | |||
ENST00000580385.1 | n.272-311C>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.634+121G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000220 AC: 5AN: 227552Hom.: 0 AF XY: 0.0000316 AC XY: 4AN XY: 126426
GnomAD4 exome AF: 0.0000408 AC: 59AN: 1447424Hom.: 0 Cov.: 47 AF XY: 0.0000416 AC XY: 30AN XY: 720536
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74332
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 | Feb 14, 2022 | - - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 796 of the RECQL4 protein (p.Glu796Lys). This variant is present in population databases (rs746005466, gnomAD 0.004%). 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: 459396). 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 expected to disrupt RECQL4 protein function with a positive 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