16-51137215-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002968.3(SALL1):c.3872A>G(p.Asn1291Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,114 control chromosomes in the GnomAD database, including 164 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 0.010 ( 14 hom., cov: 31)

Exomes 𝑓: 0.013 ( 150 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.426

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030624866).

BP6

Variant 16-51137215-T-C is Benign according to our data. Variant chr16-51137215-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 218510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51137215-T-C is described in Lovd as [Benign]. Variant chr16-51137215-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0102 (1552/152236) while in subpopulation NFE AF = 0.0164 (1117/68008). AF 95% confidence interval is 0.0156. There are 14 homozygotes in GnomAd4. There are 714 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 1552 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.3872A>G	p.Asn1291Ser	missense_variant	Exon 3 of 3	ENST00000251020.9	NP_002959.2	Q9NSC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 link	c.3872A>G	p.Asn1291Ser	missense_variant	Exon 3 of 3	1	NM_002968.3	ENSP00000251020.4		Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1554

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00338

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00903

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00707

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.00960

GnomAD2 exomes

AF:

0.0103

AC:

2583

AN:

251466

AF XY:

0.0108

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.00882

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00892

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0130

AC:

19051

AN:

1461878

Hom.:

150

Cov.:

AF XY:

0.0130

AC XY:

9478

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00926

AC:

414

AN:

44724

Gnomad4 ASJ exome

AF:

0.00432

AC:

113

AN:

26136

Gnomad4 EAS exome

AF:

0.000101

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.00765

AC:

660

AN:

86258

Gnomad4 FIN exome

AF:

0.00848

AC:

453

AN:

53420

Gnomad4 NFE exome

AF:

0.0149

AC:

16578

AN:

1111996

Gnomad4 Remaining exome

AF:

0.0106

AC:

639

AN:

60396

Heterozygous variant carriers

1166

2331

3497

4662

5828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.0102

AC:

1552

AN:

152236

Hom.:

Cov.:

AF XY:

0.00959

AC XY:

714

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00337

AC:

0.00336911

AN:

0.00336911

Gnomad4 AMR

AF:

0.00902

AC:

0.00902079

AN:

0.00902079

Gnomad4 ASJ

AF:

0.00346

AC:

0.00346021

AN:

0.00346021

Gnomad4 EAS

AF:

0.000387

AC:

0.000386698

AN:

0.000386698

Gnomad4 SAS

AF:

0.00666

AC:

0.00665834

AN:

0.00665834

Gnomad4 FIN

AF:

0.00772

AC:

0.00772273

AN:

0.00772273

Gnomad4 NFE

AF:

0.0164

AC:

0.0164245

AN:

0.0164245

Gnomad4 OTH

AF:

0.00950

AC:

0.00949668

AN:

0.00949668

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0118

Hom.:

Bravo

AF:

0.00968

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0150

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.0100

AC:

1220

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0154

EpiControl

AF:

0.0159

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 02, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SALL1: BP4, BS1, BS2 -

not specified

Benign:2

Dec 31, 2014

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Townes-Brocks syndrome 1

Benign:2

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

Townes syndrome

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.053

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0020

DANN

Benign

0.42

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.48

.;N

PROVEAN

Benign

0.66

N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0

.;B

Vest4

0.070

MPC

0.16

ClinPred

0.0018

GERP RS

-2.4

Varity_R

0.024

gMVP

0.19

Mutation Taster

=98/2

polymorphism

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