18-78992145-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_171999.4(SALL3):c.154G>T(p.Val52Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,455,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SALL3
NM_171999.4 missense
NM_171999.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 6.73
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SALL3 | NM_171999.4 | c.154G>T | p.Val52Leu | missense_variant | 2/3 | ENST00000537592.7 | NP_741996.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000846 AC: 2AN: 236386Hom.: 0 AF XY: 0.00000775 AC XY: 1AN XY: 129022
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1455018Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2AN XY: 723568
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GnomAD4 genome Cov.: 33
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33
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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 12, 2023 | The c.154G>T (p.V52L) alteration is located in exon 2 (coding exon 2) of the SALL3 gene. This alteration results from a G to T substitution at nucleotide position 154, causing the valine (V) at amino acid position 52 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;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;N
REVEL
Benign
Sift
Uncertain
.;.;D
Sift4G
Benign
T;D;D
Polyphen
1.0
.;.;D
Vest4
MutPred
Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);
MVP
MPC
0.39
ClinPred
D
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