rs754149435
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004260.4(RECQL4):c.278C>T(p.Thr93Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T93A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.278C>T | p.Thr93Met | missense_variant | 4/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.278C>T | p.Thr93Met | missense_variant | 4/21 | 1 | NM_004260.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152274Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245072Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134090
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1459780Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 5AN XY: 726182
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152274Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74394
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 26, 2024 | The c.278C>T (p.T93M) alteration is located in exon 4 (coding exon 4) of the RECQL4 gene. This alteration results from a C to T substitution at nucleotide position 278, causing the threonine (T) at amino acid position 93 to be replaced by a methionine (M). 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 | Oct 09, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 93 of the RECQL4 protein (p.Thr93Met). This variant is present in population databases (rs754149435, gnomAD 0.009%). 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: 572438). 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. 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