Genetic Variant SALL3:p.Ala117Glu (chr18-78992341-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_171999.4(SALL3):c.350C>A(p.Ala117Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.289

Publications

0 publications found

Variant links:

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]

SALL3 links:

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ACMG classification

Classification was made for transcript

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=0.052173793).

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>A	p.Ala117Glu	missense	Exon 2 of 3	NP_741996.2	Q9BXA9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SALL3	ENST00000537592.7	TSL:5 MANE Select	c.350C>A	p.Ala117Glu	missense	Exon 2 of 3	ENSP00000441823.2	Q9BXA9-1
SALL3	ENST00000575389.6	TSL:5	c.350C>A	p.Ala117Glu	missense	Exon 2 of 4	ENSP00000458360.2	Q9BXA9-2
SALL3	ENST00000536229.7	TSL:3	c.-50C>A		5_prime_UTR	Exon 1 of 3	ENSP00000439975.3	Q9BXA9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1220432

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

593144

African (AFR)

AF:

0.00

AC:

AN:

23484

American (AMR)

AF:

0.00

AC:

AN:

11506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16502

East Asian (EAS)

AF:

0.00

AC:

AN:

26692

South Asian (SAS)

AF:

0.00

AC:

AN:

56468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3904

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1002744

Other (OTH)

AF:

0.00

AC:

AN:

49558

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.36

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.027

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.22

M_CAP

Benign

0.0055

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.29

PrimateAI

Benign

0.46

PROVEAN

Benign

0.56

REVEL

Benign

0.082

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.24

Vest4

0.23

MutPred

0.15

Gain of solvent accessibility (P = 0.0456)

MVP

0.40

MPC

0.46

ClinPred

0.081

GERP RS

-2.2

Varity_R

0.053

gMVP

0.057

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over