16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCT

Position:

• chr16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCT

Variant summary

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

The NM_002968.3(SALL1):​c.475_477del​(p.Ser159del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,496,030 control chromosomes in the GnomAD database, including 74 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0079 (7 hom., cov: 31)
  • Exomes 𝑓: 0.013 (67 hom.)
• Consequence: SALL1 NM_002968.3 inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:8
• 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-CGCT-C is Benign according to our data. Variant chr16-51141744-CGCT-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195187.We mark this variant Likely_benign, oryginal submissions are: {Benign=6, Uncertain_significance=1}. Variant chr16-51141744-CGCT-C is described in Lovd as [Benign]. Variant chr16-51141744-CGCT-C is described in Lovd as [Likely_benign]. Variant chr16-51141744-CGCT-C is described in Lovd as [Benign]. Variant chr16-51141744-CGCT-C is described in Lovd as [Likely_benign]. Variant chr16-51141744-CGCT-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00795 (1200/151036) while in subpopulation NFE AF= 0.0118 (799/67672). AF 95% confidence interval is 0.0111. There are 7 homozygotes in gnomad4. There are 565 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1200 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3	c.475_477del	p.Ser159del	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.475_477del	p.Ser159del	inframe_deletion	2/3	1	NM_002968.3	ENSP00000251020	P2

Frequencies

GnomAD3 genomes AF: 0.00794 AC: 1199 AN: 150928 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00551

Gnomad AMR AF: 0.00876

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00312

Gnomad SAS AF: 0.00295

Gnomad FIN AF: 0.00777

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.00817

GnomAD3 exomes AF: 0.0128 AC: 2738 AN: 213596 Hom.: 14 AF XY: 0.0131 AC XY: 1516 AN XY: 115304

Gnomad AFR exome AF: 0.00485

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00790

Gnomad SAS exome AF: 0.00583

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0128

GnomAD4 exome AF: 0.0131 AC: 17668 AN: 1344994 Hom.: 67 AF XY: 0.0132 AC XY: 8836 AN XY: 667198

Gnomad4 AFR exome AF: 0.00319

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.00215

Gnomad4 SAS exome AF: 0.00467

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.00795 AC: 1200 AN: 151036 Hom.: 7 Cov.: 31 AF XY: 0.00766 AC XY: 565 AN XY: 73776

Gnomad4 AFR AF: 0.00231

Gnomad4 AMR AF: 0.00874

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.00313

Gnomad4 SAS AF: 0.00296

Gnomad4 FIN AF: 0.00777

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.00809

Bravo AF: 0.00835

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:8

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 21, 2016	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	SALL1: BS1, BS2 -

Townes-Brocks syndrome 1 Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	May 31, 2017	- -

Townes syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs113614842; hg19: chr16-51175655;