8-144514501-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004260.4(RECQL4):āc.1645A>Cā(p.Lys549Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,611,896 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K549E) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.1645A>C | p.Lys549Gln | missense_variant | 10/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1645A>C | p.Lys549Gln | missense_variant | 10/21 | 1 | NM_004260.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152062Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000487 AC: 12AN: 246512Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134310
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1459718Hom.: 0 Cov.: 36 AF XY: 0.0000151 AC XY: 11AN XY: 726110
GnomAD4 genome AF: 0.000118 AC: 18AN: 152178Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8AN XY: 74408
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 549 of the RECQL4 protein (p.Lys549Gln). This variant is present in population databases (rs542466006, gnomAD 0.07%). 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: 528969). 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. - |
RECQL4-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 27, 2022 | The RECQL4 c.1645A>C variant is predicted to result in the amino acid substitution p.Lys549Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.063% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-145739885-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at