rs374898583
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_004260.4(RECQL4):āc.2743A>Gā(p.Met915Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,603,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2743A>G | p.Met915Val | missense_variant | 15/21 | ENST00000617875.6 | NP_004251.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2743A>G | p.Met915Val | missense_variant | 15/21 | 1 | NM_004260.4 | ENSP00000482313.2 | ||
RECQL4 | ENST00000621189.4 | c.1672A>G | p.Met558Val | missense_variant | 14/20 | 1 | ENSP00000483145.1 | |||
RECQL4 | ENST00000534626.6 | c.913A>G | p.Met305Val | missense_variant | 6/8 | 5 | ENSP00000477457.1 | |||
ENSG00000265393 | ENST00000580385.1 | n.271+22T>C | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152218Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000130 AC: 3AN: 231466Hom.: 0 AF XY: 0.00000794 AC XY: 1AN XY: 126008
GnomAD4 exome AF: 0.0000152 AC: 22AN: 1451386Hom.: 0 Cov.: 67 AF XY: 0.00000971 AC XY: 7AN XY: 721140
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152218Hom.: 0 Cov.: 34 AF XY: 0.0000672 AC XY: 5AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 25, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The RECQL4 p.Met915Val variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs374898583) and ClinVar (classified as uncertain significance by Invitae for Baller-Gerold syndrome). The variant was also identified in control databases in 3 of 231466 chromosomes at a frequency of 0.000013 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 13596 chromosomes (freq: 0.000074), Latino in 1 of 32644 chromosomes (freq: 0.000031) and European (non-Finnish) in 1 of 103854 chromosomes (freq: 0.00001), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. The p.Met915 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Baller-Gerold syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at