rs13336129

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002968.3(SALL1):c.475A>G(p.Ser159Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,243,758 control chromosomes in the GnomAD database, including 3,526 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S159R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.066 ( 382 hom., cov: 31)

Exomes 𝑓: 0.098 ( 3144 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0900

Variant links:

Genes affected

SALL1 (HGNC:10524): (spalt like transcription factor 1) The protein encoded by this gene is a zinc finger transcriptional repressor and may be part of the NuRD histone deacetylase complex (HDAC). Defects in this gene are a cause of Townes-Brocks syndrome (TBS) as well as bronchio-oto-renal syndrome (BOR). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SALL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002341956).

BP6

Variant 16-51141747-T-C is Benign according to our data. Variant chr16-51141747-T-C is described in ClinVar as [Benign]. Clinvar id is 258875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51141747-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL1	NM_002968.3 linkuse as main transcript	c.475A>G	p.Ser159Gly	missense_variant	2/3	ENST00000251020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL1	ENST00000251020.9 linkuse as main transcript	c.475A>G	p.Ser159Gly	missense_variant	2/3	1	NM_002968.3	P2	Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.0658

AC:

9726

AN:

147732

Hom.:

382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0537

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.0214

Gnomad SAS

AF:

0.0225

Gnomad FIN

AF:

0.0879

Gnomad MID

AF:

0.0229

Gnomad NFE

AF:

0.0841

Gnomad OTH

AF:

0.0414

GnomAD3 exomes

AF:

0.0679

AC:

12552

AN:

184844

Hom.:

297

AF XY:

0.0685

AC XY:

6867

AN XY:

100214

show subpopulations

Gnomad AFR exome

AF:

0.0622

Gnomad AMR exome

AF:

0.0375

Gnomad ASJ exome

AF:

0.0459

Gnomad EAS exome

AF:

0.0297

Gnomad SAS exome

AF:

0.0345

Gnomad FIN exome

AF:

0.0885

Gnomad NFE exome

AF:

0.0897

Gnomad OTH exome

AF:

0.0763

GnomAD4 exome

AF:

0.0981

AC:

107547

AN:

1095922

Hom.:

3144

Cov.:

AF XY:

0.0972

AC XY:

52536

AN XY:

540650

show subpopulations

Gnomad4 AFR exome

AF:

0.0671

Gnomad4 AMR exome

AF:

0.0454

Gnomad4 ASJ exome

AF:

0.0523

Gnomad4 EAS exome

AF:

0.0362

Gnomad4 SAS exome

AF:

0.0395

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.0905

GnomAD4 genome

AF:

0.0658

AC:

9728

AN:

147836

Hom.:

382

Cov.:

AF XY:

0.0646

AC XY:

4670

AN XY:

72256

show subpopulations

Gnomad4 AFR

AF:

0.0536

Gnomad4 AMR

AF:

0.0376

Gnomad4 ASJ

AF:

0.0377

Gnomad4 EAS

AF:

0.0215

Gnomad4 SAS

AF:

0.0226

Gnomad4 FIN

AF:

0.0879

Gnomad4 NFE

AF:

0.0841

Gnomad4 OTH

AF:

0.0410

Alfa

AF:

0.0762

Hom.:

147

Bravo

AF:

0.0618

ESP6500AA

AF:

0.0461

AC:

201

ESP6500EA

AF:

0.0630

AC:

540

ExAC

AF:

0.0592

AC:

6302

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Townes syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Townes-Brocks syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetics and Molecular Pathology, SA Pathology

May 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

Cadd

Benign

0.73

Dann

Benign

0.21

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.32

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.43

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.45

T;T;.

Polyphen

0.034

.;B;.

Vest4

0.090

MPC

0.18

ClinPred

0.0027

GERP RS

-0.37

Varity_R

0.041

gMVP

0.12

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