Genetic Variant NM_171999.4:c.8G>C (chr18-78980282-G-C) – 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.8G>C(p.Arg3Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000162 in 1,231,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40

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=0.41302693).

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.8G>C	p.Arg3Pro	missense	Exon 1 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.8G>C	p.Arg3Pro	missense	Exon 1 of 3	ENSP00000441823.2	Q9BXA9-1
SALL3	ENST00000575389.6	TSL:5	c.8G>C	p.Arg3Pro	missense	Exon 1 of 4	ENSP00000458360.2	Q9BXA9-2
SALL3	ENST00000925065.1		c.8G>C	p.Arg3Pro	missense	Exon 1 of 3	ENSP00000595124.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000162

AC:

AN:

1231518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

605258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24808

American (AMR)

AF:

0.00

AC:

AN:

24414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20366

East Asian (EAS)

AF:

0.00

AC:

AN:

24648

South Asian (SAS)

AF:

0.00

AC:

AN:

65506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3438

European-Non Finnish (NFE)

AF:

0.00000202

AC:

AN:

988254

Other (OTH)

AF:

0.00

AC:

AN:

48550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.030

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.73

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.2

PhyloP100

6.4

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0090

Polyphen

0.0020

Vest4

0.51

MutPred

0.42

Gain of glycosylation at R3 (P = 0.016)

MVP

0.68

MPC

0.57

ClinPred

0.98

GERP RS

-2.0

PromoterAI

0.045

Neutral

(source)

Varity_R

0.65

gMVP

0.21

Mutation Taster

=62/38

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