18-78992443-C-A

Variant names:

• chr18-78992443-C-A
• NM_171999.4:c.452C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_171999.4(SALL3):​c.452C>A​(p.Ala151Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000004 in 1,250,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: SALL3 NM_171999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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]

ACMG classification

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=0.07189128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL3	NM_171999.4	c.452C>A	p.Ala151Asp	missense_variant	Exon 2 of 3	ENST00000537592.7	NP_741996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL3	ENST00000537592.7	c.452C>A	p.Ala151Asp	missense_variant	Exon 2 of 3	5	NM_171999.4	ENSP00000441823.2
SALL3	ENST00000575389.6	c.452C>A	p.Ala151Asp	missense_variant	Exon 2 of 4	5		ENSP00000458360.2
SALL3	ENST00000536229.7	c.53C>A	p.Ala18Asp	missense_variant	Exon 1 of 3	3		ENSP00000439975.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000400 AC: 5 AN: 1250534 Hom.: 0 Cov.: 30 AF XY: 0.00000650 AC XY: 4 AN XY: 615582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000492

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.83
DEOGEN2	Benign	0.029	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.31	T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.62	.;N;.
REVEL	Benign	0.030
Sift	Benign	0.47	.;T;.
Sift4G	Benign	0.63	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.19
MutPred		0.12		Gain of solvent accessibility (P = 0.1154);Gain of solvent accessibility (P = 0.1154);.;
MVP		0.43
MPC		0.60
ClinPred		0.081	T
GERP RS		-1.4
Varity_R		0.079
gMVP		0.17

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: chr18-76752443;