16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_002968.3(SALL1):c.460_477dupAGCAGCAGCAGCAGCAGC(p.Ser154_Ser159dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,579,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002968.3 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000662 AC: 1AN: 151000Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.0000224 AC: 32AN: 1428924Hom.: 0 Cov.: 43 AF XY: 0.0000281 AC XY: 20AN XY: 710696
GnomAD4 genome AF: 0.00000662 AC: 1AN: 151000Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1AN XY: 73702
ClinVar
Submissions by phenotype
not provided Uncertain:2
In-frame insertion of 6 amino acids in a repetitive region with no known function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -
The SALL1 p.Ser57_Ser62dup variant was not identified in the literature nor was it identified in dbSNP, ClinVar, Cosmic, LOVD 3.0 or in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (March 6, 2019, v2.1.1).This variant is an in-frame duplication resulting in the duplication of serine (Ser) residues between codons 57 to 62; the impact of this alteration on SALL1 protein function is not known. The variant also occurs outside of the splicing consensus sequence and three of four 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. -
Townes-Brocks syndrome 1 Uncertain:1
The inframe insertion variant c.460_477dupp.Ser154_Ser159dup in SALL1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel not in any individuals in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, study on multiple affected individuals and functional impact of the variant is not available. This variant p.Ser154_Ser159dup causes duplication of amino acid Serine at postion 154 and Serine at postion 159. For these reasons, this variant has been classified as Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at