8-144514050-G-GTGTGGC
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4
The NM_004260.4(RECQL4):c.1935_1936insGCCACA(p.Ala644_Thr645dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000769 in 1,430,902 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T645T) has been classified as Likely benign.
Frequency
Consequence
NM_004260.4 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.1935_1936insGCCACA | p.Ala644_Thr645dup | inframe_insertion | 12/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1935_1936insGCCACA | p.Ala644_Thr645dup | inframe_insertion | 12/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.864_865insGCCACA | p.Ala287_Thr288dup | inframe_insertion | 11/20 | 1 | |||
RECQL4 | ENST00000532846.2 | c.790_791insGCCACA | p.Ala263_Thr264dup | inframe_insertion | 8/9 | 5 | |||
RECQL4 | ENST00000534626.6 | c.304_305insGCCACA | p.Ala101_Thr102dup | inframe_insertion | 3/8 | 5 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 0.00000769 AC: 11AN: 1430902Hom.: 0 Cov.: 36 AF XY: 0.00000846 AC XY: 6AN XY: 709276
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 26, 2022 | Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with Rothmund-Thomson syndrome (PMID: 27247962). This variant is not present in population databases (gnomAD no frequency). This variant, c.1930_1935dup, is a complex sequence change that results in the insertion of 2 amino acid(s) in the RECQL4 protein (p.Ala644_Thr645dup). 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