rs13336129

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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:5

Conservation

PhyloP100: -0.0900

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

Townes-Brocks syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Townes-Brocks syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SALL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 258875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.475A>G	p.Ser159Gly	missense_variant	Exon 2 of 3	ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 link	c.475A>G	p.Ser159Gly	missense_variant	Exon 2 of 3	1	NM_002968.3	ENSP00000251020.4

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

GnomAD2 exomes

AF:

0.0679

AC:

12552

AN:

184844

AF XY:

0.0685

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 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

African (AFR)

AF:

0.0671

AC:

1679

AN:

25030

American (AMR)

AF:

0.0454

AC:

1328

AN:

29244

Ashkenazi Jewish (ASJ)

AF:

0.0523

AC:

917

AN:

17530

East Asian (EAS)

AF:

0.0362

AC:

924

AN:

25494

South Asian (SAS)

AF:

0.0395

AC:

2259

AN:

57216

European-Finnish (FIN)

AF:

0.116

AC:

4420

AN:

37986

Middle Eastern (MID)

AF:

0.0383

AC:

158

AN:

4122

European-Non Finnish (NFE)

AF:

0.107

AC:

91913

AN:

855662

Other (OTH)

AF:

0.0905

AC:

3949

AN:

43638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

5915

11830

17745

23660

29575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3382

6764

10146

13528

16910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0658

AC:

9728

AN:

147836

Hom.:

382

Cov.:

AF XY:

0.0646

AC XY:

4670

AN XY:

72256

show subpopulations

African (AFR)

AF:

0.0536

AC:

2186

AN:

40754

American (AMR)

AF:

0.0376

AC:

559

AN:

14854

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

127

AN:

3372

East Asian (EAS)

AF:

0.0215

AC:

110

AN:

5128

South Asian (SAS)

AF:

0.0226

AC:

107

AN:

4742

European-Finnish (FIN)

AF:

0.0879

AC:

897

AN:

10204

Middle Eastern (MID)

AF:

0.0211

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0841

AC:

5513

AN:

65548

Other (OTH)

AF:

0.0410

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

458

916

1374

1832

2290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Townes syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Townes-Brocks syndrome 1

Benign:1

May 28, 2020

Genetics and Molecular Pathology, SA Pathology

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.23

.;T;T

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

MutationAssessor

Benign

-0.34

.;N;.

PhyloP100

-0.090

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over