16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCT

Position:

• chr16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_002968.3(SALL1):​c.469_477delAGCAGCAGC​(p.Ser157_Ser159del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,580,006 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0037 (20 hom.)
• Consequence: SALL1 NM_002968.3 conservative_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:9
• Conservation: PhyloP100: 1.79

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 -9 ACMG points.

• BP6: Variant 16-51141744-CGCTGCTGCT-C is Benign according to our data. Variant chr16-51141744-CGCTGCTGCT-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 224343.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3, Benign=2}. Variant chr16-51141744-CGCTGCTGCT-C is described in Lovd as [Likely_benign]. Variant chr16-51141744-CGCTGCTGCT-C is described in Lovd as [Likely_benign]. Variant chr16-51141744-CGCTGCTGCT-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00234 (354/151106) while in subpopulation NFE AF= 0.00386 (261/67694). AF 95% confidence interval is 0.00347. There are 0 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 354 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3	c.469_477delAGCAGCAGC	p.Ser157_Ser159del	conservative_inframe_deletion	2/3	ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9	c.469_477delAGCAGCAGC	p.Ser157_Ser159del	conservative_inframe_deletion	2/3	1	NM_002968.3	ENSP00000251020.4

Frequencies

GnomAD3 genomes AF: 0.00234 AC: 354 AN: 150996 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000877

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00237

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00144

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00386

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00285 AC: 609 AN: 213596 Hom.: 1 AF XY: 0.00281 AC XY: 324 AN XY: 115304

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.00274

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000389

Gnomad FIN exome AF: 0.00124

Gnomad NFE exome AF: 0.00452

Gnomad OTH exome AF: 0.00470

GnomAD4 exome AF: 0.00369 AC: 5270 AN: 1428900 Hom.: 20 AF XY: 0.00361 AC XY: 2564 AN XY: 710684

Gnomad4 AFR exome AF: 0.000825

Gnomad4 AMR exome AF: 0.00216

Gnomad4 ASJ exome AF: 0.00259

Gnomad4 EAS exome AF: 0.0000779

Gnomad4 SAS exome AF: 0.0000476

Gnomad4 FIN exome AF: 0.00160

Gnomad4 NFE exome AF: 0.00443

Gnomad4 OTH exome AF: 0.00291

GnomAD4 genome AF: 0.00234 AC: 354 AN: 151106 Hom.: 0 Cov.: 31 AF XY: 0.00230 AC XY: 170 AN XY: 73818

Gnomad4 AFR AF: 0.000875

Gnomad4 AMR AF: 0.00237

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00144

Gnomad4 NFE AF: 0.00386

Gnomad4 OTH AF: 0.00190

Bravo AF: 0.00230

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:9

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:6

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 17, 2021	This variant is associated with the following publications: (PMID: 27657687) -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	SALL1: BS1, BS2 -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 09, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 30, 2016	- -

Townes-Brocks syndrome 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

-

- -

Townes syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 14, 2021

- -

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;