chr18-78994245-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_171999.4(SALL3):​c.2254G>A​(p.Val752Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

3
11
5

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.83

Publications

1 publications found
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 18-78994245-G-A is Benign according to our data. Variant chr18-78994245-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 221917.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SALL3NM_171999.4 linkc.2254G>A p.Val752Met missense_variant Exon 2 of 3 ENST00000537592.7 NP_741996.2 Q9BXA9-1A9JR48A0A384MEH2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SALL3ENST00000537592.7 linkc.2254G>A p.Val752Met missense_variant Exon 2 of 3 5 NM_171999.4 ENSP00000441823.2 Q9BXA9-1
SALL3ENST00000575389.6 linkc.2254G>A p.Val752Met missense_variant Exon 2 of 4 5 ENSP00000458360.2 Q9BXA9-2
SALL3ENST00000536229.7 linkc.1855G>A p.Val619Met missense_variant Exon 1 of 3 3 ENSP00000439975.3 Q9BXA9-3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
250334
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461382
Hom.:
0
Cov.:
89
AF XY:
0.00000413
AC XY:
3
AN XY:
727006
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26114
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86248
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53000
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000270
AC:
3
AN:
1111976
Other (OTH)
AF:
0.00
AC:
0
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.0000624
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1
Jan 01, 2013
Paul Sabatier University EA-4555, Paul Sabatier University
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
27
DANN
Uncertain
0.98
DEOGEN2
Benign
0.089
T;.;T;.
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.60
D;D;D;D
MetaSVM
Uncertain
0.033
D
MutationAssessor
Benign
1.0
.;L;L;.
PhyloP100
6.8
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-2.3
.;.;N;.
REVEL
Uncertain
0.46
Sift
Benign
0.051
.;.;T;.
Sift4G
Uncertain
0.040
D;D;D;D
Polyphen
1.0
.;.;D;.
Vest4
0.67
MutPred
0.50
.;Gain of MoRF binding (P = 0.0798);Gain of MoRF binding (P = 0.0798);.;
MVP
0.88
MPC
1.2
ClinPred
0.87
D
GERP RS
5.2
Varity_R
0.17
gMVP
0.39

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

Other links and lift over

dbSNP: rs760494400; hg19: chr18-76754245; COSMIC: COSV73306376; COSMIC: COSV73306376; API