Genetic Variant SALL3:p.Asp141Asn (chr18-78992412-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_171999.4(SALL3):c.421G>A(p.Asp141Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,330,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.18775815).

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.421G>A	p.Asp141Asn	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.421G>A	p.Asp141Asn	missense	Exon 2 of 3	ENSP00000441823.2	Q9BXA9-1
SALL3	ENST00000575389.6	TSL:5	c.421G>A	p.Asp141Asn	missense	Exon 2 of 4	ENSP00000458360.2	Q9BXA9-2
SALL3	ENST00000536229.7	TSL:3	c.22G>A	p.Asp8Asn	missense	Exon 1 of 3	ENSP00000439975.3	Q9BXA9-3

Frequencies

GnomAD3 genomes

AF:

0.0000598

AC:

AN:

150396

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000464

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:

0.000485

GnomAD2 exomes

AF:

0.00

AC:

AN:

3194

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

AF:

0.0000288

AC:

AN:

1180114

Hom.:

Cov.:

AF XY:

0.0000244

AC XY:

AN XY:

574774

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22054

American (AMR)

AF:

0.000124

AC:

AN:

8086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14586

East Asian (EAS)

AF:

0.00

AC:

AN:

23578

South Asian (SAS)

AF:

0.00

AC:

AN:

52096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3216

European-Non Finnish (NFE)

AF:

0.0000265

AC:

AN:

981120

Other (OTH)

AF:

0.000149

AC:

AN:

47128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

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

AF:

0.0000598

AC:

AN:

150396

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73386

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41262

American (AMR)

AF:

0.000464

AC:

AN:

15102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67388

Other (OTH)

AF:

0.000485

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000831

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

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.037

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.62

M_CAP

Benign

0.016

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

PhyloP100

7.6

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.55

REVEL

Benign

0.17

Sift

Benign

0.33

Sift4G

Benign

0.47

Polyphen

0.50

Vest4

0.36

MutPred

0.11

Gain of glycosylation at P145 (P = 0.1556)

MVP

0.54

MPC

0.38

ClinPred

0.71

GERP RS

3.9

Varity_R

0.091

gMVP

0.095

Mutation Taster

=82/18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over