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GeneBe

18-78992770-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_171999.4(SALL3):c.779G>C(p.Gly260Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,037,688 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

1
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13644761).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SALL3NM_171999.4 linkuse as main transcriptc.779G>C p.Gly260Ala missense_variant 2/3 ENST00000537592.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SALL3ENST00000537592.7 linkuse as main transcriptc.779G>C p.Gly260Ala missense_variant 2/35 NM_171999.4 P1Q9BXA9-1
SALL3ENST00000575389.6 linkuse as main transcriptc.779G>C p.Gly260Ala missense_variant 2/45 Q9BXA9-2
SALL3ENST00000536229.7 linkuse as main transcriptc.380G>C p.Gly127Ala missense_variant 1/33 Q9BXA9-3

Frequencies

GnomAD3 genomes
AF:
0.000226
AC:
33
AN:
146168
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000735
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000425
Gnomad OTH
AF:
0.000995
GnomAD4 exome
AF:
0.000436
AC:
389
AN:
891520
Hom.:
0
Cov.:
28
AF XY:
0.000422
AC XY:
176
AN XY:
416698
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000389
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000124
Gnomad4 NFE exome
AF:
0.000472
Gnomad4 OTH exome
AF:
0.000295
GnomAD4 genome
AF:
0.000226
AC:
33
AN:
146168
Hom.:
1
Cov.:
32
AF XY:
0.000211
AC XY:
15
AN XY:
71044
show subpopulations
Gnomad4 AFR
AF:
0.0000735
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000425
Gnomad4 OTH
AF:
0.000995
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000261

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 GeneticsAug 11, 2022The c.779G>C (p.G260A) alteration is located in exon 2 (coding exon 2) of the SALL3 gene. This alteration results from a G to C substitution at nucleotide position 779, causing the glycine (G) at amino acid position 260 to be replaced by an alanine (A). 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
0.088
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
Cadd
Benign
17
Dann
Benign
0.65
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.50
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.64
T;T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.89
L;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Pathogenic
0.81
D
Sift4G
Benign
0.48
T;T;T
Polyphen
0.30
.;B;.
Vest4
0.31
MutPred
0.17
Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);.;
MVP
0.43
MPC
0.43
ClinPred
0.25
T
GERP RS
3.5
Varity_R
0.085
gMVP
0.43

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: rs1018465445; hg19: chr18-76752770; API