Genetic Variant SALL3:p.Ala117Gly (chr18-78992341-C-G) – 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>G(p.Ala117Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000492 in 1,220,432 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.05249268).

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>G	p.Ala117Gly	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>G	p.Ala117Gly	missense	Exon 2 of 3	ENSP00000441823.2	Q9BXA9-1
SALL3	ENST00000575389.6	TSL:5	c.350C>G	p.Ala117Gly	missense	Exon 2 of 4	ENSP00000458360.2	Q9BXA9-2
SALL3	ENST00000536229.7	TSL:3	c.-50C>G		5_prime_UTR	Exon 1 of 3	ENSP00000439975.3	Q9BXA9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000492

AC:

AN:

1220432

Hom.:

Cov.:

AF XY:

0.00000674

AC XY:

AN XY:

593144

show subpopulations

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:

0.00000499

AC:

AN:

1002744

Other (OTH)

AF:

0.0000202

AC:

AN:

49558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.8

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.18

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.24

M_CAP

Benign

0.0041

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

PhyloP100

0.29

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.99

REVEL

Benign

0.075

Sift

Benign

0.42

Sift4G

Benign

0.40

Polyphen

0.0020

Vest4

0.091

MutPred

0.18

Loss of helix (P = 0.079)

MVP

0.16

MPC

0.40

ClinPred

0.040

GERP RS

-2.2

Varity_R

0.039

gMVP

0.036

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over