Genetic Variant SALL3:p.Leu67Met (chr18-78992190-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_171999.4(SALL3):c.199C>A(p.Leu67Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000021 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3542444).

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.199C>A	p.Leu67Met	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.199C>A	p.Leu67Met	missense	Exon 2 of 3	ENSP00000441823.2	Q9BXA9-1
SALL3	ENST00000536229.7	TSL:3	c.-201C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000439975.3	Q9BXA9-3
SALL3	ENST00000575389.6	TSL:5	c.199C>A	p.Leu67Met	missense	Exon 2 of 4	ENSP00000458360.2	Q9BXA9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

242318

AF XY:

0.0000227

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000224

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458208

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33294

American (AMR)

AF:

0.00

AC:

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26040

East Asian (EAS)

AF:

0.0000760

AC:

AN:

39488

South Asian (SAS)

AF:

0.00

AC:

AN:

85950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111160

Other (OTH)

AF:

0.00

AC:

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

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

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.021

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.63

M_CAP

Benign

0.015

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.3

PhyloP100

1.6

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.2

REVEL

Benign

0.21

Sift

Uncertain

0.011

Sift4G

Benign

0.24

Polyphen

1.0

Vest4

0.52

MutPred

0.40

Loss of helix (P = 0.0626)

MVP

0.61

MPC

0.38

ClinPred

0.13

GERP RS

3.7

Varity_R

0.088

gMVP

0.012

Mutation Taster

=92/8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over