chr8-144513948-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004260.4(RECQL4):āc.2038A>Gā(p.Met680Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,558,008 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M680I) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2038A>G | p.Met680Val | missense_variant | 12/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2038A>G | p.Met680Val | missense_variant | 12/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.967A>G | p.Met323Val | missense_variant | 11/20 | 1 | |||
RECQL4 | ENST00000534626.6 | c.409A>G | p.Met137Val | missense_variant | 3/8 | 5 | |||
RECQL4 | ENST00000532846.2 | c.895A>G | p.Met299Val | missense_variant | 8/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151494Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000123 AC: 2AN: 162620Hom.: 0 AF XY: 0.0000228 AC XY: 2AN XY: 87824
GnomAD4 exome AF: 7.11e-7 AC: 1AN: 1406396Hom.: 0 Cov.: 36 AF XY: 0.00000144 AC XY: 1AN XY: 694828
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151612Hom.: 0 Cov.: 34 AF XY: 0.0000270 AC XY: 2AN XY: 74048
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 680 of the RECQL4 protein (p.Met680Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 574063). 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