rs1085307143
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_002968.3(SALL1):c.1108_1109del(p.Val370LeufsTer19) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SALL1
NM_002968.3 frameshift
NM_002968.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.16
Genes affected
SALL1 (HGNC:10524): (spalt like transcription factor 1) The protein encoded by this gene is a zinc finger transcriptional repressor and may be part of the NuRD histone deacetylase complex (HDAC). Defects in this gene are a cause of Townes-Brocks syndrome (TBS) as well as bronchio-oto-renal syndrome (BOR). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 29 pathogenic variants in the truncated region.
PP5
?
Variant 16-51141112-GAC-G is Pathogenic according to our data. Variant chr16-51141112-GAC-G is described in ClinVar as [Pathogenic]. Clinvar id is 426114.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SALL1 | NM_002968.3 | c.1108_1109del | p.Val370LeufsTer19 | frameshift_variant | 2/3 | ENST00000251020.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SALL1 | ENST00000251020.9 | c.1108_1109del | p.Val370LeufsTer19 | frameshift_variant | 2/3 | 1 | NM_002968.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Townes-Brocks syndrome 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Geisinger Autism and Developmental Medicine Institute, Geisinger Health System | Apr 26, 2017 | The following ACMG criteria are met: PVS1 (Predicted null variant in gene with LOF mechanism of disease), PM2 (Absent from population databases), PP4 (Patient's phenotype is specific for gene). The patient's clinical presentation is consistent with Townes-Brockes syndrome (anal stenosis, dysplastic ears, autism, developmental delays, sleep disturbance). A renal ultrasound found small kidneys with punctate echogenic foci bilaterally, and nephrology diagnosed him with chronic kidney disease stage 3. He had a normal cardiology evaluation. Brain MRI showed delayed myelination. His mother, who carries this variant, required speech therapy as a child. She has a history of kidney stones, but had normal renal ultrasound and cardiology evaluations. - |
Computational scores
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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