rs594821

Variant names:

• chr18-78985589-C-T
• rs594821
• NM_171999.4:c.82+5233C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_171999.4(SALL3):​c.82+5233C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,082 control chromosomes in the GnomAD database, including 858 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (858 hom., cov: 33)
• Consequence: SALL3 NM_171999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL3	NM_171999.4	c.82+5233C>T		intron_variant	Intron 1 of 2	ENST00000537592.7	NP_741996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL3	ENST00000537592.7	c.82+5233C>T		intron_variant	Intron 1 of 2	5	NM_171999.4	ENSP00000441823.2
SALL3	ENST00000575389.6	c.82+5233C>T		intron_variant	Intron 1 of 3	5		ENSP00000458360.2
SALL3	ENST00000572928.1	n.61+519C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15319 AN: 151964 Hom.: 855 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.0761

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15349 AN: 152082 Hom.: 858 Cov.: 33 AF XY: 0.0979 AC XY: 7283 AN XY: 74370

African (AFR) AF: 0.156 AC: 6481 AN: 41454

American (AMR) AF: 0.0511 AC: 782 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0721 AC: 250 AN: 3468

East Asian (EAS) AF: 0.0757 AC: 391 AN: 5162

South Asian (SAS) AF: 0.119 AC: 574 AN: 4814

European-Finnish (FIN) AF: 0.0775 AC: 821 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5776 AN: 67988

Other (OTH) AF: 0.107 AC: 225 AN: 2108

Alfa AF: 0.0871 Hom.: 1119

Bravo AF: 0.0998

Asia WGS AF: 0.122 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.72
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs594821; hg19: chr18-76745589;