rs746200109
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004260.4(RECQL4):c.903A>T(p.Glu301Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign 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. E301K) has been classified as Likely benign.
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.903A>T | p.Glu301Asp | missense_variant | 5/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.903A>T | p.Glu301Asp | missense_variant | 5/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.-169A>T | 5_prime_UTR_variant | 4/20 | 1 | ||||
RECQL4 | ENST00000524998.1 | c.426A>T | p.Glu142Asp | missense_variant | 3/4 | 3 | |||
RECQL4 | ENST00000534538.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 247912Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134968
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460942Hom.: 0 Cov.: 66 AF XY: 0.00000413 AC XY: 3AN XY: 726742
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 301 of the RECQL4 protein (p.Glu301Asp). This variant is present in population databases (rs746200109, gnomAD 0.0009%). 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: 529003). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | May 27, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at