rs1286553686
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004260.4(RECQL4):c.1778C>T(p.Ala593Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,611,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict 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. A593D) 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.1778C>T | p.Ala593Val | missense_variant | 11/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1778C>T | p.Ala593Val | missense_variant | 11/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.707C>T | p.Ala236Val | missense_variant | 10/20 | 1 | |||
RECQL4 | ENST00000534626.6 | c.149C>T | p.Ala50Val | missense_variant | 2/8 | 5 | |||
RECQL4 | ENST00000532846.2 | c.635C>T | p.Ala212Val | missense_variant | 7/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 34
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459004Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 725748
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2023 | The c.1778C>T (p.A593V) alteration is located in exon 11 (coding exon 11) of the RECQL4 gene. This alteration results from a C to T substitution at nucleotide position 1778, causing the alanine (A) at amino acid position 593 to be replaced by a valine (V). 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 | Jun 02, 2023 | 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. 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 not expected to disrupt RECQL4 protein function. ClinVar contains an entry for this variant (Variation ID: 2197276). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 593 of the RECQL4 protein (p.Ala593Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at