Variant chr18-78992181-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_171999.4(SALL3):c.190G>A(p.Ala64Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,610,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.349

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059206128).

BP6

Variant 18-78992181-G-A is Benign according to our data. Variant chr18-78992181-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3316044.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL3	NM_171999.4 linkuse as main transcript	c.190G>A	p.Ala64Thr	missense_variant	2/3	ENST00000537592.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL3	ENST00000537592.7 linkuse as main transcript	c.190G>A	p.Ala64Thr	missense_variant	2/3	5	NM_171999.4	P1	Q9BXA9-1
SALL3	ENST00000575389.6 linkuse as main transcript	c.190G>A	p.Ala64Thr	missense_variant	2/4	5			Q9BXA9-2
SALL3	ENST00000536229.7 linkuse as main transcript	c.-210G>A		5_prime_UTR_variant	1/3	3			Q9BXA9-3
SALL3	ENST00000572928.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000867

AC:

AN:

242160

Hom.:

AF XY:

0.0000908

AC XY:

AN XY:

132228

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000144

AC:

210

AN:

1458056

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

105

AN XY:

725312

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.000105

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000840

Hom.:

Bravo

AF:

0.000106

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000579

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.0

DANN

Benign

0.94

DEOGEN2

Benign

0.0094

T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

.;N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.27

.;.;N

REVEL

Benign

0.056

Sift

Benign

0.31

.;.;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.17

MVP

0.19

MPC

0.38

ClinPred

0.032

GERP RS

-4.2

Varity_R

0.022

gMVP

0.023

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over