18-78992208-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_171999.4(SALL3):​c.217T>A​(p.Cys73Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SALL3
NM_171999.4 missense

Scores

8
6
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.88
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SALL3NM_171999.4 linkuse as main transcriptc.217T>A p.Cys73Ser missense_variant 2/3 ENST00000537592.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SALL3ENST00000537592.7 linkuse as main transcriptc.217T>A p.Cys73Ser missense_variant 2/35 NM_171999.4 P1Q9BXA9-1
SALL3ENST00000575389.6 linkuse as main transcriptc.217T>A p.Cys73Ser missense_variant 2/45 Q9BXA9-2
SALL3ENST00000536229.7 linkuse as main transcriptc.-183T>A 5_prime_UTR_variant 1/33 Q9BXA9-3
SALL3ENST00000572928.1 linkuse as main transcript downstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Benign
23
DANN
Benign
0.95
DEOGEN2
Benign
0.034
T;.;D
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D;T;T
M_CAP
Benign
0.069
D
MetaRNN
Pathogenic
0.89
D;D;D
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Pathogenic
3.4
.;M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-8.4
.;.;D
REVEL
Uncertain
0.56
Sift
Pathogenic
0.0
.;.;D
Sift4G
Benign
0.32
T;D;D
Polyphen
1.0
.;.;D
Vest4
0.88
MutPred
0.67
Gain of glycosylation at C73 (P = 0.0243);Gain of glycosylation at C73 (P = 0.0243);Gain of glycosylation at C73 (P = 0.0243);
MVP
0.72
MPC
0.49
ClinPred
1.0
D
GERP RS
4.6
Varity_R
0.94
gMVP
0.083

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-76752208; API