16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCT

Variant names:

• chr16-51141744-CGCT-C
• rs113614842
• NM_002968.3:c.475_477delAGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3 BP6 BS1 BS2

The NM_002968.3(SALL1):​c.475_477delAGC​(p.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 0.0126 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 conservative_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:8
• Conservation: PhyloP100: 1.79
• Publications: 2 publications found

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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
• Townes-Brocks syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002968.3
• 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 VariationId is 195187.
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1200 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002968.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.475_477delAGC	p.Ser159del	conservative_inframe_deletion	Exon 2 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.184_186delAGC	p.Ser62del	conservative_inframe_deletion	Exon 2 of 3	NP_001121364.1	Q9NSC2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.475_477delAGC	p.Ser159del	conservative_inframe_deletion	Exon 2 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000566102.1	TSL:1	c.77-4195_77-4193delAGC		intron	N/A	ENSP00000455582.1	H3BQ32
	SALL1	ENST00000440970.6	TSL:5	c.475_477delAGC	p.Ser159del	conservative_inframe_deletion	Exon 3 of 4	ENSP00000407914.2	Q9NSC2-1

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

GnomAD2 exomes AF: 0.0128 AC: 2738 AN: 213596 AF XY: 0.0131

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 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

African (AFR) AF: 0.00319 AC: 99 AN: 31002

American (AMR) AF: 0.0111 AC: 440 AN: 39708

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 293 AN: 23180

East Asian (EAS) AF: 0.00215 AC: 74 AN: 34424

South Asian (SAS) AF: 0.00467 AC: 359 AN: 76888

European-Finnish (FIN) AF: 0.0102 AC: 485 AN: 47586

Middle Eastern (MID) AF: 0.00570 AC: 29 AN: 5092

European-Non Finnish (NFE) AF: 0.0147 AC: 15197 AN: 1032324

Other (OTH) AF: 0.0126 AC: 692 AN: 54790

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

African (AFR) AF: 0.00231 AC: 95 AN: 41132

American (AMR) AF: 0.00874 AC: 133 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3448

East Asian (EAS) AF: 0.00313 AC: 16 AN: 5116

South Asian (SAS) AF: 0.00296 AC: 14 AN: 4734

European-Finnish (FIN) AF: 0.00777 AC: 81 AN: 10422

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0118 AC: 799 AN: 67672

Other (OTH) AF: 0.00809 AC: 17 AN: 2102

Alfa AF: 0.0205 Hom.: 0

Bravo AF: 0.00835

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	1	1	Townes-Brocks syndrome 1 (2)
-	-	1	Townes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs113614842; hg19: chr16-51175655; COSMIC: COSV51756543; COSMIC: COSV51756543;