rs764549158
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004260.4(RECQL4):c.2419C>T(p.Arg807Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,592,090 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 (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
RECQL4
NM_004260.4 missense
NM_004260.4 missense
Scores
7
4
1
Clinical Significance
Conservation
PhyloP100: 2.23
Genes affected
RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.841
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2419C>T | p.Arg807Cys | missense_variant | 14/21 | ENST00000617875.6 | NP_004251.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2419C>T | p.Arg807Cys | missense_variant | 14/21 | 1 | NM_004260.4 | ENSP00000482313.2 | ||
RECQL4 | ENST00000621189.4 | c.1348C>T | p.Arg450Cys | missense_variant | 13/20 | 1 | ENSP00000483145.1 | |||
RECQL4 | ENST00000534626.6 | c.634-124C>T | intron_variant | 5 | ENSP00000477457.1 | |||||
ENSG00000265393 | ENST00000580385.1 | n.272-344G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151840Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000138 AC: 3AN: 217598Hom.: 0 AF XY: 0.0000165 AC XY: 2AN XY: 121358
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GnomAD4 exome AF: 0.0000104 AC: 15AN: 1440136Hom.: 0 Cov.: 48 AF XY: 0.0000140 AC XY: 10AN XY: 715980
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151954Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74268
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 10, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 807 of the RECQL4 protein (p.Arg807Cys). 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: 459399). 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 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
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
DEOGEN2
Uncertain
D;D
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MutationAssessor
Pathogenic
.;H
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MVP
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at