rs754977025
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004260.4(RECQL4):c.2665G>A(p.Ala889Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000767 in 1,577,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2665G>A | p.Ala889Thr | missense_variant | 15/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2665G>A | p.Ala889Thr | missense_variant | 15/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.1594G>A | p.Ala532Thr | missense_variant | 14/20 | 1 | |||
ENST00000580385.1 | n.271+100C>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.838G>A | p.Ala280Thr | missense_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152244Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000369 AC: 7AN: 189910Hom.: 0 AF XY: 0.0000390 AC XY: 4AN XY: 102484
GnomAD4 exome AF: 0.0000828 AC: 118AN: 1424872Hom.: 0 Cov.: 67 AF XY: 0.0000780 AC XY: 55AN XY: 705480
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152244Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74376
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 889 of the RECQL4 protein (p.Ala889Thr). This variant is present in population databases (rs754977025, 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: 239744). 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 with a negative predictive value of 80%. 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