8-144515218-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004260.4(RECQL4):c.1415C>A(p.Ala472Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000019 in 1,578,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A472F) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.1415C>A | p.Ala472Asp | missense_variant | 8/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1415C>A | p.Ala472Asp | missense_variant | 8/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.344C>A | p.Ala115Asp | missense_variant | 7/20 | 1 | |||
RECQL4 | ENST00000532846.2 | c.302C>A | p.Ala101Asp | missense_variant | 4/9 | 5 | |||
RECQL4 | ENST00000688394.1 | n.438C>A | non_coding_transcript_exon_variant | 2/4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000140 AC: 2AN: 1426180Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 706438
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2020 | This sequence change replaces alanine with aspartic acid at codon 472 of the RECQL4 protein (p.Ala472Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RECQL4-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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