Variant 18-78992521-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_171999.4(SALL3):c.530C>T(p.Ala177Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000471 in 1,486,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.62

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL3	NM_171999.4 linkuse as main transcript	c.530C>T	p.Ala177Val	missense_variant	2/3	ENST00000537592.7	NP_741996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL3	ENST00000537592.7 linkuse as main transcript	c.530C>T	p.Ala177Val	missense_variant	2/3	5	NM_171999.4	ENSP00000441823	P1	Q9BXA9-1
SALL3	ENST00000575389.6 linkuse as main transcript	c.530C>T	p.Ala177Val	missense_variant	2/4	5		ENSP00000458360		Q9BXA9-2
SALL3	ENST00000536229.7 linkuse as main transcript	c.131C>T	p.Ala44Val	missense_variant	1/3	3		ENSP00000439975		Q9BXA9-3

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

149516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

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:

0.0000448

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000224

AC:

AN:

1336758

Hom.:

Cov.:

AF XY:

0.00000303

AC XY:

AN XY:

661082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000263

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.46e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72886

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000664

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000448

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000639

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.530C>T (p.A177V) alteration is located in exon 2 (coding exon 2) of the SALL3 gene. This alteration results from a C to T substitution at nucleotide position 530, causing the alanine (A) at amino acid position 177 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Uncertain

0.62

.;D;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Pathogenic

3.1

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.4

.;D;.

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

.;D;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.81

MutPred

0.58

Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);.;

MVP

0.81

MPC

0.39

ClinPred

0.68

GERP RS

3.9

Varity_R

0.75

gMVP

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over