rs496809

Positions:

• chr18-78996673-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_171999.4(SALL3):​c.3472-218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,262 control chromosomes in the GnomAD database, including 988 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 0.096 (988 hom., cov: 33)
• Consequence: SALL3 NM_171999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL3	NM_171999.4	c.3472-218C>T		intron_variant		ENST00000537592.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL3	ENST00000537592.7	c.3472-218C>T		intron_variant		5	NM_171999.4	P1
SALL3	ENST00000536229.7	c.2857-218C>T		intron_variant		3
SALL3	ENST00000573324.1	c.449+1211C>T		intron_variant		3
SALL3	ENST00000575389.6	c.3256-218C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14546 AN: 152144 Hom.: 985 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.0476

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0957 AC: 14574 AN: 152262 Hom.: 988 Cov.: 33 AF XY: 0.0914 AC XY: 6806 AN XY: 74456

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0478

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.0598

Gnomad4 SAS AF: 0.0478

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0657

Gnomad4 OTH AF: 0.0856

Alfa AF: 0.0728 Hom.: 228

Bravo AF: 0.0991

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs496809; hg19: chr18-76756673;