chr16-51141007-A-AG
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002968.3(SALL1):c.1214_1215insC(p.Leu406PhefsTer32) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.98
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 12 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 27 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-51141007-A-AG is Pathogenic according to our data. Variant chr16-51141007-A-AG is described in ClinVar as [Pathogenic]. Clinvar id is 459257.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.1214_1215insC | p.Leu406PhefsTer32 | frameshift_variant | 2/3 | ENST00000251020.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SALL1 | ENST00000251020.9 | c.1214_1215insC | p.Leu406PhefsTer32 | frameshift_variant | 2/3 | 1 | NM_002968.3 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 53
GnomAD4 exome
Cov.:
53
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 syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2016 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in SALL1 are known to be pathogenic (PMID: 9973281, 16088922). This sequence change inserts 1 nucleotide in exon 2 of the SALL1 mRNA (c.1214dupC), causing a frameshift at codon 406. This creates a premature translational stop signal (p.Leu406Phefs*32) and is expected to result in an absent or disrupted protein product. - |
Computational scores
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Calibrated prediction
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Prediction
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