chr8-144516302-C-T
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004260.4(RECQL4):c.817G>A(p.Ala273Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,609,868 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A273V) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
Publications
- Baller-Gerold syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
- Rothmund-Thomson syndromeInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Rothmund-Thomson syndrome type 2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
- osteosarcomaInheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
- rapadilino syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000591 AC: 90AN: 152224Hom.: 0 Cov.: 34 show subpopulations
GnomAD2 exomes AF: 0.000307 AC: 74AN: 241366 AF XY: 0.000250 show subpopulations
GnomAD4 exome AF: 0.000152 AC: 221AN: 1457526Hom.: 0 Cov.: 66 AF XY: 0.000145 AC XY: 105AN XY: 724810 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000591 AC: 90AN: 152342Hom.: 0 Cov.: 34 AF XY: 0.000564 AC XY: 42AN XY: 74484 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:1
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Hereditary cancer-predisposing syndrome Uncertain:1
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Baller-Gerold syndrome Benign:1
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RECQL4-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at