16-51139648-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002968.3(SALL1):c.2574C>T(p.Leu858Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,613,246 control chromosomes in the GnomAD database, including 338,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 23760 hom., cov: 33)

Exomes 𝑓: 0.65 ( 314595 hom. )

Consequence

SALL1
NM_002968.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.39

Publications

32 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-51139648-G-A is Benign according to our data. Variant chr16-51139648-G-A is described in ClinVar as Benign. ClinVar VariationId is 258866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002968.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.2574C>T	p.Leu858Leu	synonymous	Exon 2 of 3	NP_002959.2
	SALL1	NM_001127892.2		c.2283C>T	p.Leu761Leu	synonymous	Exon 2 of 3	NP_001121364.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SALL1	ENST00000251020.9	TSL:1 MANE Select	c.2574C>T	p.Leu858Leu	synonymous	Exon 2 of 3	ENSP00000251020.4
SALL1	ENST00000566102.1	TSL:1	c.77-2096C>T		intron	N/A	ENSP00000455582.1
SALL1	ENST00000440970.6	TSL:5	c.2574C>T	p.Leu858Leu	synonymous	Exon 3 of 4	ENSP00000407914.2

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78718

AN:

151988

Hom.:

23755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.606

Gnomad ASJ

AF:

0.526

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.735

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.532

GnomAD2 exomes

AF:

0.626

AC:

157353

AN:

251370

AF XY:

0.638

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.653

Gnomad ASJ exome

AF:

0.522

Gnomad EAS exome

AF:

0.708

Gnomad FIN exome

AF:

0.632

Gnomad NFE exome

AF:

0.649

Gnomad OTH exome

AF:

0.623

GnomAD4 exome

AF:

0.650

AC:

950250

AN:

1461140

Hom.:

314595

Cov.:

AF XY:

0.654

AC XY:

475254

AN XY:

726798

show subpopulations

African (AFR)

AF:

0.165

AC:

5519

AN:

33436

American (AMR)

AF:

0.649

AC:

28988

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

13602

AN:

26128

East Asian (EAS)

AF:

0.728

AC:

28891

AN:

39684

South Asian (SAS)

AF:

0.733

AC:

63199

AN:

86252

European-Finnish (FIN)

AF:

0.635

AC:

33928

AN:

53416

Middle Eastern (MID)

AF:

0.477

AC:

2747

AN:

5760

European-Non Finnish (NFE)

AF:

0.662

AC:

735423

AN:

1111386

Other (OTH)

AF:

0.629

AC:

37953

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

20969

41938

62906

83875

104844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19046

38092

57138

76184

95230

<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:

0.518

AC:

78721

AN:

152106

Hom.:

23760

Cov.:

AF XY:

0.523

AC XY:

38875

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.183

AC:

7603

AN:

41502

American (AMR)

AF:

0.607

AC:

9276

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

1828

AN:

3472

East Asian (EAS)

AF:

0.714

AC:

3683

AN:

5156

South Asian (SAS)

AF:

0.735

AC:

3533

AN:

4808

European-Finnish (FIN)

AF:

0.618

AC:

6544

AN:

10592

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.653

AC:

44402

AN:

67972

Other (OTH)

AF:

0.532

AC:

1123

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1648

3296

4945

6593

8241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.577

Hom.:

17048

Bravo

AF:

0.501

Asia WGS

AF:

0.698

AC:

2424

AN:

3478

EpiCase

AF:

0.640

EpiControl

AF:

0.638

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Townes-Brocks syndrome 1

Benign:4

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jun 21, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Nov 24, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Townes syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.047

(source)

DANN

Benign

0.49

PhyloP100

-2.4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over