18-78992460-C-G

Position:

chr18-78992460-C-G

Variant summary

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

The NM_171999.4(SALL3):c.469C>G(p.Pro157Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000377 in 1,436,824 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

SALL3
NM_171999.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.88

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=0.04893449).

BP6

Variant 18-78992460-C-G is Benign according to our data. Variant chr18-78992460-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2344434.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL3	NM_171999.4 linkuse as main transcript	c.469C>G	p.Pro157Ala	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.469C>G	p.Pro157Ala	missense_variant	2/3	5	NM_171999.4	ENSP00000441823	P1	Q9BXA9-1
SALL3	ENST00000575389.6 linkuse as main transcript	c.469C>G	p.Pro157Ala	missense_variant	2/4	5		ENSP00000458360		Q9BXA9-2
SALL3	ENST00000536229.7 linkuse as main transcript	c.70C>G	p.Pro24Ala	missense_variant	1/3	3		ENSP00000439975		Q9BXA9-3

Frequencies

GnomAD3 genomes

AF:

0.000233

AC:

AN:

149912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000728

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:

0.000446

Gnomad OTH

AF:

0.000969

GnomAD3 exomes

AF:

0.000193

AC:

AN:

67372

Hom.:

AF XY:

0.000153

AC XY:

AN XY:

39264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000157

Gnomad ASJ exome

AF:

0.000173

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000406

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000394

AC:

507

AN:

1286912

Hom.:

Cov.:

AF XY:

0.000383

AC XY:

243

AN XY:

634650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000220

Gnomad4 ASJ exome

AF:

0.0000948

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000124

Gnomad4 NFE exome

AF:

0.000470

Gnomad4 OTH exome

AF:

0.000210

GnomAD4 genome

AF:

0.000233

AC:

AN:

149912

Hom.:

Cov.:

AF XY:

0.000219

AC XY:

AN XY:

73098

show subpopulations

Gnomad4 AFR

AF:

0.0000728

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:

0.000446

Gnomad4 OTH

AF:

0.000969

Alfa

AF:

0.0000693

Hom.:

Bravo

AF:

0.000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.0

DANN

Benign

0.65

DEOGEN2

Benign

0.045

.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.41

T;T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.20

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.34

.;N;.

REVEL

Benign

0.031

Sift

Benign

0.44

.;T;.

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.091

MutPred

0.14

Loss of glycosylation at P157 (P = 0.0099);Loss of glycosylation at P157 (P = 0.0099);.;

MVP

0.19

MPC

0.38

ClinPred

0.036

GERP RS

0.83

Varity_R

0.022

gMVP

0.11

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