rs753254336
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004260.4(RECQL4):c.2134G>A(p.Asp712Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,591,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D712E) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2134G>A | p.Asp712Asn | missense_variant | 13/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2134G>A | p.Asp712Asn | missense_variant | 13/21 | 1 | NM_004260.4 | P1 | |
ENST00000580385.1 | n.303C>T | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000379 AC: 8AN: 211082Hom.: 0 AF XY: 0.0000262 AC XY: 3AN XY: 114598
GnomAD4 exome AF: 0.0000188 AC: 27AN: 1439666Hom.: 0 Cov.: 47 AF XY: 0.0000210 AC XY: 15AN XY: 714236
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74312
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 712 of the RECQL4 protein (p.Asp712Asn). This variant is present in population databases (rs753254336, gnomAD 0.02%). 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: 406899). 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. 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