Variant 18-78980335-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_171999.4(SALL3):c.61C>T(p.Pro21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,290,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.406

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04083529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL3	NM_171999.4 linkuse as main transcript	c.61C>T	p.Pro21Ser	missense_variant	1/3	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.61C>T	p.Pro21Ser	missense_variant	1/3	5	NM_171999.4	ENSP00000441823	P1	Q9BXA9-1
SALL3	ENST00000575389.6 linkuse as main transcript	c.61C>T	p.Pro21Ser	missense_variant	1/4	5		ENSP00000458360		Q9BXA9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1290038

Hom.:

Cov.:

AF XY:

0.00000944

AC XY:

AN XY:

635764

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000438

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000293

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 25, 2023

The c.61C>T (p.P21S) alteration is located in exon 1 (coding exon 1) of the SALL3 gene. This alteration results from a C to T substitution at nucleotide position 61, causing the proline (P) at amino acid position 21 to be replaced by a serine (S). 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

Benign

0.076

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0081

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.42

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.14

.;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.010

.;.;N

REVEL

Benign

0.070

Sift

Benign

0.79

.;.;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.061

MutPred

0.17

Loss of catalytic residue at P20 (P = 0.0131);Loss of catalytic residue at P20 (P = 0.0131);Loss of catalytic residue at P20 (P = 0.0131);

MVP

0.13

MPC

0.40

ClinPred

0.044

GERP RS

0.64

Varity_R

0.050

gMVP

0.066

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