16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCT

Variant names:

• chr16-51141744-C-CGCT
• rs113614842
• NM_002968.3:c.475_477dupAGC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002968.3(SALL1):​c.475_477dupAGC​(p.Ser159dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,579,498 control chromosomes in the GnomAD database, including 444 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (289 hom., cov: 31)
  • Exomes 𝑓: 0.020 (155 hom.)
• Consequence: SALL1 NM_002968.3 conservative_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.34

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 16-51141744-C-CGCT is Benign according to our data. Variant chr16-51141744-C-CGCT is described in ClinVar as [Likely_benign]. Clinvar id is 258874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3	c.475_477dupAGC	p.Ser159dup	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	c.475_477dupAGC	p.Ser159dup	conservative_inframe_insertion	Exon 2 of 3	1	NM_002968.3	ENSP00000251020.4

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6342 AN: 150958 Hom.: 284 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.00354

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0375

GnomAD3 exomes AF: 0.0240 AC: 5119 AN: 213596 Hom.: 25 AF XY: 0.0219 AC XY: 2530 AN XY: 115304

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.0182

Gnomad ASJ exome AF: 0.0305

Gnomad EAS exome AF: 0.0220

Gnomad SAS exome AF: 0.0193

Gnomad FIN exome AF: 0.00468

Gnomad NFE exome AF: 0.0186

Gnomad OTH exome AF: 0.0207

GnomAD4 exome AF: 0.0198 AC: 28257 AN: 1428430 Hom.: 155 Cov.: 43 AF XY: 0.0192 AC XY: 13635 AN XY: 710460

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.0297

Gnomad4 EAS exome AF: 0.0207

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.00407

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0261

GnomAD4 genome AF: 0.0422 AC: 6368 AN: 151068 Hom.: 289 Cov.: 31 AF XY: 0.0403 AC XY: 2972 AN XY: 73796

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.0190

Gnomad4 SAS AF: 0.0192

Gnomad4 FIN AF: 0.00354

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0385

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Townes-Brocks syndrome 1 Benign:4

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Jan 10, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 20, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2014

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Aug 17, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 33226606) -

-

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Townes syndrome Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113614842; hg19: chr16-51175655;