chr8-144514988-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_004260.4(RECQL4):c.1568G>A(p.Ser523Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,611,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 8/13 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. S523T) has been classified as Likely benign.
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.1568G>A | p.Ser523Asn | missense_variant | 9/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1568G>A | p.Ser523Asn | missense_variant | 9/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.497G>A | p.Ser166Asn | missense_variant | 8/20 | 1 | |||
RECQL4 | ENST00000532846.2 | c.425G>A | p.Ser142Asn | missense_variant | 5/9 | 5 | |||
RECQL4 | ENST00000688394.1 | n.591G>A | non_coding_transcript_exon_variant | 3/4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000533 AC: 13AN: 244018Hom.: 0 AF XY: 0.0000750 AC XY: 10AN XY: 133330
GnomAD4 exome AF: 0.0000295 AC: 43AN: 1459332Hom.: 0 Cov.: 33 AF XY: 0.0000386 AC XY: 28AN XY: 725822
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74356
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2022 | 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: 647761). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is present in population databases (rs754735053, gnomAD 0.04%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 523 of the RECQL4 protein (p.Ser523Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at