16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCTGCT

Position:

• chr16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

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

The NM_002968.3(SALL1):​c.472_477dupAGCAGC​(p.Ser158_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 0.00205 in 1,579,948 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0098 (31 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (7 hom.)
• Consequence: SALL1 NM_002968.3 conservative_inframe_insertion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:7
• 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 -9 ACMG points.

• BP6: Variant 16-51141744-C-CGCTGCT is Benign according to our data. Variant chr16-51141744-C-CGCTGCT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 319615.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=4}.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00979 (1479/151100) while in subpopulation AFR AF= 0.0334 (1372/41132). AF 95% confidence interval is 0.0319. There are 31 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1479 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3	c.472_477dupAGCAGC	p.Ser158_Ser159dup	conservative_inframe_insertion	2/3	ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9	c.472_477dupAGCAGC	p.Ser158_Ser159dup	conservative_inframe_insertion	2/3	1	NM_002968.3	ENSP00000251020.4

Frequencies

GnomAD3 genomes AF: 0.00978 AC: 1476 AN: 150990 Hom.: 31 Cov.: 31

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00408

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000780

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.000478

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00625

GnomAD3 exomes AF: 0.00288 AC: 615 AN: 213596 Hom.: 3 AF XY: 0.00222 AC XY: 256 AN XY: 115304

Gnomad AFR exome AF: 0.0309

Gnomad AMR exome AF: 0.00235

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000653

Gnomad SAS exome AF: 0.00210

Gnomad FIN exome AF: 0.000646

Gnomad NFE exome AF: 0.000423

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.00124 AC: 1766 AN: 1428848 Hom.: 7 Cov.: 43 AF XY: 0.00106 AC XY: 755 AN XY: 710654

Gnomad4 AFR exome AF: 0.0341

Gnomad4 AMR exome AF: 0.00214

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00278

Gnomad4 SAS exome AF: 0.00167

Gnomad4 FIN exome AF: 0.000443

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.00979 AC: 1479 AN: 151100 Hom.: 31 Cov.: 31 AF XY: 0.00996 AC XY: 735 AN XY: 73818

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.00407

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000782

Gnomad4 SAS AF: 0.00106

Gnomad4 FIN AF: 0.000478

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.00618

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:7

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 02, 2015	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SALL1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 07, 2019	- -

Townes-Brocks syndrome 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Townes syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

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;