18-78992145-G-T

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

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.73
Variant links:
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]

Genome browser will be placed here

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
SALL3NM_171999.4 linkc.154G>T p.Val52Leu missense_variant 2/3 ENST00000537592.7 NP_741996.2 Q9BXA9-1A9JR48A0A384MEH2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SALL3ENST00000537592.7 linkc.154G>T p.Val52Leu missense_variant 2/35 NM_171999.4 ENSP00000441823.2 Q9BXA9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000846
AC:
2
AN:
236386
Hom.:
0
AF XY:
0.00000775
AC XY:
1
AN XY:
129022
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000297
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000946
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1455018
Hom.:
0
Cov.:
29
AF XY:
0.00000276
AC XY:
2
AN XY:
723568
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000226
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsJul 12, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T;.;T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.8
.;M;M
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-2.2
.;.;N
REVEL
Benign
0.20
Sift
Uncertain
0.0070
.;.;D
Sift4G
Benign
0.25
T;D;D
Polyphen
1.0
.;.;D
Vest4
0.55
MutPred
0.41
Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);
MVP
0.69
MPC
0.39
ClinPred
0.86
D
GERP RS
4.4
Varity_R
0.23
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1296338924; hg19: chr18-76752145; API