8-144515989-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004260.4(RECQL4):c.1130A>T(p.Gln377Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,609,516 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. Q377R) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense, splice_region
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.1130A>T | p.Gln377Leu | missense_variant, splice_region_variant | 5/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1130A>T | p.Gln377Leu | missense_variant, splice_region_variant | 5/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.59A>T | p.Gln20Leu | missense_variant, splice_region_variant | 4/20 | 1 | |||
RECQL4 | ENST00000532846.2 | c.17A>T | p.Gln6Leu | missense_variant, splice_region_variant | 1/9 | 5 | |||
RECQL4 | ENST00000524998.1 | c.653A>T | p.Gln218Leu | missense_variant, splice_region_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152188Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000812 AC: 2AN: 246404Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134224
GnomAD4 exome AF: 0.00000686 AC: 10AN: 1457328Hom.: 0 Cov.: 65 AF XY: 0.00000276 AC XY: 2AN XY: 724250
GnomAD4 genome AF: 0.0000986 AC: 15AN: 152188Hom.: 0 Cov.: 34 AF XY: 0.0000941 AC XY: 7AN XY: 74352
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2020 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Baller-Gerold syndrome;C1849453:Rapadilino syndrome;C5203410:Rothmund-Thomson syndrome type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 16, 2022 | - - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2022 | This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 377 of the RECQL4 protein (p.Gln377Leu). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 528980). 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