8-144516377-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004260.4(RECQL4):c.742C>T(p.Arg248Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,610,242 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. R248H) has been classified 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.742C>T | p.Arg248Cys | missense_variant | 5/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.742C>T | p.Arg248Cys | missense_variant | 5/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.-330C>T | 5_prime_UTR_variant | 4/20 | 1 | ||||
RECQL4 | ENST00000524998.1 | c.265C>T | p.Arg89Cys | missense_variant | 3/4 | 3 | |||
RECQL4 | ENST00000534538.1 | c.*546C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152220Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000205 AC: 5AN: 243940Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133302
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1457904Hom.: 0 Cov.: 65 AF XY: 0.0000124 AC XY: 9AN XY: 725222
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152338Hom.: 0 Cov.: 34 AF XY: 0.000107 AC XY: 8AN XY: 74486
ClinVar
Submissions by phenotype
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 | Feb 07, 2022 | - - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 248 of the RECQL4 protein (p.Arg248Cys). This variant is present in population databases (rs540719285, gnomAD 0.02%). 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: 572686). 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. 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