chr18-78996673-C-T

Variant names:

• chr18-78996673-C-T
• rs496809
• NM_171999.4:c.3472-218C>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.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
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_171999.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL3	NM_171999.4	MANE Select	c.3472-218C>T		intron	N/A	NP_741996.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL3	ENST00000537592.7	TSL:5 MANE Select	c.3472-218C>T		intron	N/A	ENSP00000441823.2
	SALL3	ENST00000575389.6	TSL:5	c.3256-218C>T		intron	N/A	ENSP00000458360.2
	SALL3	ENST00000536229.7	TSL:3	c.2857-218C>T		intron	N/A	ENSP00000439975.3

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

African (AFR) AF: 0.191 AC: 7932 AN: 41526

American (AMR) AF: 0.0478 AC: 732 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3470

East Asian (EAS) AF: 0.0598 AC: 310 AN: 5182

South Asian (SAS) AF: 0.0478 AC: 231 AN: 4830

European-Finnish (FIN) AF: 0.0568 AC: 603 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0657 AC: 4469 AN: 68018

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.0739 Hom.: 267

Bravo AF: 0.0991

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.47
PhyloP100		-0.19
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: rs496809; hg19: chr18-76756673;