dbSNP rs778464569: SALL3:p.Pro149Ala (chr18-78992436-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.445C>G(p.Pro149Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000729 in 1,371,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.000075 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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:

Genome browser will be placed here

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=0.04984051).

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.445C>G	p.Pro149Ala	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.445C>G	p.Pro149Ala	missense	Exon 2 of 3	ENSP00000441823.2	Q9BXA9-1
SALL3	ENST00000575389.6	TSL:5	c.445C>G	p.Pro149Ala	missense	Exon 2 of 4	ENSP00000458360.2	Q9BXA9-2
SALL3	ENST00000536229.7	TSL:3	c.46C>G	p.Pro16Ala	missense	Exon 1 of 3	ENSP00000439975.3	Q9BXA9-3

Frequencies

GnomAD3 genomes

AF:

0.0000600

AC:

AN:

149962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000134

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000476

AC:

AN:

20988

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000579

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000745

AC:

AN:

1221268

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

599098

show subpopulations

African (AFR)

AF:

0.0000442

AC:

AN:

22606

American (AMR)

AF:

0.0000921

AC:

AN:

10854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16776

East Asian (EAS)

AF:

0.00

AC:

AN:

24096

South Asian (SAS)

AF:

0.00

AC:

AN:

60716

European-Finnish (FIN)

AF:

0.0000667

AC:

AN:

29994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3396

European-Non Finnish (NFE)

AF:

0.0000867

AC:

AN:

1003848

Other (OTH)

AF:

0.00

AC:

AN:

48982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000600

AC:

AN:

149962

Hom.:

Cov.:

AF XY:

0.0000547

AC XY:

AN XY:

73160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41220

American (AMR)

AF:

0.00

AC:

AN:

15074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000134

AC:

AN:

67248

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.00

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000177

AC:

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

0.048

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.046

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.42

M_CAP

Benign

0.0081

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

PhyloP100

4.8

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.23

REVEL

Benign

0.088

Sift

Benign

0.92

Sift4G

Benign

0.51

Polyphen

0.0070

Vest4

0.29

MutPred

0.15

Loss of glycosylation at P149 (P = 0.0065)

MVP

0.25

MPC

0.38

ClinPred

0.98

GERP RS

0.98

Varity_R

0.019

gMVP

0.11

Mutation Taster

=95/5

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