18-78992341-C-T

Variant names:

• chr18-78992341-C-T
• rs1193337415
• NM_171999.4:c.350C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_171999.4(SALL3):​c.350C>T​(p.Ala117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 151,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A117G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SALL3 NM_171999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056789517).

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.350C>T	p.Ala117Val	missense	Exon 2 of 3	NP_741996.2	Q9BXA9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL3	ENST00000537592.7	TSL:5 MANE Select	c.350C>T	p.Ala117Val	missense	Exon 2 of 3	ENSP00000441823.2	Q9BXA9-1
	SALL3	ENST00000575389.6	TSL:5	c.350C>T	p.Ala117Val	missense	Exon 2 of 4	ENSP00000458360.2	Q9BXA9-2
	SALL3	ENST00000536229.7	TSL:3	c.-50C>T		5_prime_UTR	Exon 1 of 3	ENSP00000439975.3	Q9BXA9-3

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 151032 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 16358 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1220432 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 593144

African (AFR) AF: 0.00 AC: 0 AN: 23484

American (AMR) AF: 0.00 AC: 0 AN: 11506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16502

East Asian (EAS) AF: 0.00 AC: 0 AN: 26692

South Asian (SAS) AF: 0.00 AC: 0 AN: 56468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3904

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1002744

Other (OTH) AF: 0.00 AC: 0 AN: 49558

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 151032 Hom.: 0 Cov.: 33 AF XY: 0.0000407 AC XY: 3 AN XY: 73774

African (AFR) AF: 0.00 AC: 0 AN: 41206

American (AMR) AF: 0.000264 AC: 4 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67706

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.84
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.64	N
PhyloP100		0.29
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.063
Sift	Benign	0.32	T
Sift4G	Benign	0.38	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0404)
MVP		0.37
MPC		0.39
ClinPred		0.080	T
GERP RS		-2.2
Varity_R		0.032
gMVP		0.056
Mutation Taster		=99/1	polymorphism

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: rs1193337415; hg19: chr18-76752341;