rs140827311
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002968.3(SALL1):c.809C>T(p.Pro270Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000533 in 1,614,132 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00092 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 6 hom. )
Consequence
SALL1
NM_002968.3 missense
NM_002968.3 missense
Scores
5
11
Clinical Significance
Conservation
PhyloP100: 6.41
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005468607).
BP6
?
Variant 16-51141413-G-A is Benign according to our data. Variant chr16-51141413-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 282089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51141413-G-A is described in Lovd as [Benign]. Variant chr16-51141413-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000919 (140/152334) while in subpopulation EAS AF= 0.0224 (116/5178). AF 95% confidence interval is 0.0191. There are 1 homozygotes in gnomad4. There are 75 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 140 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SALL1 | NM_002968.3 | c.809C>T | p.Pro270Leu | missense_variant | 2/3 | ENST00000251020.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SALL1 | ENST00000251020.9 | c.809C>T | p.Pro270Leu | missense_variant | 2/3 | 1 | NM_002968.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000920 AC: 140AN: 152214Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00163 AC: 410AN: 251432Hom.: 4 AF XY: 0.00143 AC XY: 195AN XY: 135900
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GnomAD4 exome AF: 0.000493 AC: 721AN: 1461798Hom.: 6 Cov.: 53 AF XY: 0.000477 AC XY: 347AN XY: 727192
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GnomAD4 genome ? AF: 0.000919 AC: 140AN: 152334Hom.: 1 Cov.: 32 AF XY: 0.00101 AC XY: 75AN XY: 74486
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Asia WGS
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3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 04, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 19, 2015 | - - |
Townes syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;.
Polyphen
0.047
.;B;.
Vest4
MVP
MPC
0.24
ClinPred
T
GERP RS
Varity_R
gMVP
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