8-144514485-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004260.4(RECQL4):c.1661A>G(p.His554Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,098 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. H554L) 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.1661A>G | p.His554Arg | missense_variant | 10/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1661A>G | p.His554Arg | missense_variant | 10/21 | 1 | NM_004260.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000809 AC: 2AN: 247078Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134574
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460034Hom.: 0 Cov.: 36 AF XY: 0.00000551 AC XY: 4AN XY: 726288
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74262
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 04, 2022 | The c.1661A>G (p.H554R) alteration is located in exon 10 (coding exon 10) of the RECQL4 gene. This alteration results from a A to G substitution at nucleotide position 1661, causing the histidine (H) at amino acid position 554 to be replaced by an arginine (R). 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 | Jun 11, 2022 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 554 of the RECQL4 protein (p.His554Arg). This variant is present in population databases (rs779426316, gnomAD 0.002%). 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: 459339). 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