16-51141732-TGCCGCC-TGCCGCCGCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_002968.3(SALL1):c.487_489dupGGC(p.Gly163dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,610,550 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 1 hom. )

Consequence

SALL1
NM_002968.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 2.36

Publications

0 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 -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_002968.3

BP6

Variant 16-51141732-T-TGCC is Benign according to our data. Variant chr16-51141732-T-TGCC is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 258877.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00128 (193/150964) while in subpopulation AFR AF = 0.00231 (94/40642). AF 95% confidence interval is 0.00193. There are 0 homozygotes in GnomAd4. There are 99 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 193 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.487_489dupGGC	p.Gly163dup	conservative_inframe_insertion	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.487_489dupGGC	p.Gly163dup	conservative_inframe_insertion	Exon 2 of 3	1	NM_002968.3	ENSP00000251020.4

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

193

AN:

150846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000657

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.000421

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000958

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000792

AC:

197

AN:

248582

AF XY:

0.000735

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.000551

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000723

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000872

AC:

1273

AN:

1459586

Hom.:

Cov.:

AF XY:

0.000898

AC XY:

652

AN XY:

726078

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00189

AC:

AN:

33378

American (AMR)

AF:

0.000716

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00310

AC:

AN:

26126

East Asian (EAS)

AF:

0.00197

AC:

AN:

39688

South Asian (SAS)

AF:

0.000674

AC:

AN:

86058

European-Finnish (FIN)

AF:

0.0000939

AC:

AN:

53274

Middle Eastern (MID)

AF:

0.00184

AC:

AN:

5438

European-Non Finnish (NFE)

AF:

0.000773

AC:

859

AN:

1110664

Other (OTH)

AF:

0.00144

AC:

AN:

60256

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.399

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00128

AC:

193

AN:

150964

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

AN XY:

73812

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

40642

American (AMR)

AF:

0.000656

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00318

AC:

AN:

3454

East Asian (EAS)

AF:

0.00116

AC:

AN:

5156

South Asian (SAS)

AF:

0.000421

AC:

AN:

4748

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000958

AC:

AN:

67840

Other (OTH)

AF:

0.00143

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000546

Hom.:

EpiCase

AF:

0.00158

EpiControl

AF:

0.000654

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 11, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 21, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SALL1: BS1 -

Townes-Brocks syndrome 1

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Townes syndrome

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.4

Mutation Taster

=74/26

polymorphism

(source)

Splicing

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