18-78992284-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_171999.4(SALL3):c.293C>T(p.Ser98Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000655 in 1,527,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
SALL3
NM_171999.4 missense
NM_171999.4 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 5.46
Genes affected
SALL3 (HGNC:10527): (spalt like transcription factor 3) This gene encodes a sal-like C2H2-type zinc-finger protein, and belongs to a family of evolutionarily conserved genes found in species as diverse as Drosophila, C. elegans, and vertebrates. Mutations in some of these genes are associated with congenital disorders in human, suggesting their importance in embryonic development. This protein binds to DNA methyltransferase 3 alpha (DNMT3A), and reduces DNMT3A-mediated CpG island methylation. It is suggested that silencing of this gene, resulting in acceleration of DNA methylation, may have a role in oncogenesis. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37708905).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SALL3 | NM_171999.4 | c.293C>T | p.Ser98Leu | missense_variant | 2/3 | ENST00000537592.7 | NP_741996.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SALL3 | ENST00000537592.7 | c.293C>T | p.Ser98Leu | missense_variant | 2/3 | 5 | NM_171999.4 | ENSP00000441823.2 | ||
SALL3 | ENST00000536229 | c.-107C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/3 | 3 | ENSP00000439975.3 | ||||
SALL3 | ENST00000575389.6 | c.293C>T | p.Ser98Leu | missense_variant | 2/4 | 5 | ENSP00000458360.2 | |||
SALL3 | ENST00000536229 | c.-107C>T | 5_prime_UTR_variant | 1/3 | 3 | ENSP00000439975.3 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151798Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000685 AC: 10AN: 146072Hom.: 0 AF XY: 0.0000963 AC XY: 8AN XY: 83060
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GnomAD4 exome AF: 0.0000676 AC: 93AN: 1375912Hom.: 0 Cov.: 30 AF XY: 0.0000647 AC XY: 44AN XY: 679870
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GnomAD4 genome AF: 0.0000461 AC: 7AN: 151798Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74126
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 02, 2024 | The c.293C>T (p.S98L) alteration is located in exon 2 (coding exon 2) of the SALL3 gene. This alteration results from a C to T substitution at nucleotide position 293, causing the serine (S) at amino acid position 98 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D
REVEL
Benign
Sift
Benign
.;T
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
Loss of phosphorylation at S98 (P = 9e-04);Loss of phosphorylation at S98 (P = 9e-04);
MVP
MPC
0.35
ClinPred
T
GERP RS
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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