chr16-51141744-CGCTGCTGCT-C

Variant names:

• chr16-51141744-CGCTGCTGCT-C
• rs113614842
• NM_002968.3:c.469_477delAGCAGCAGC

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.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). Synonymous variant affecting the same amino acid position (i.e. S157S) has been classified as Likely benign.

• 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
• 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-CGCTGCTGCT-C is Benign according to our data. Variant chr16-51141744-CGCTGCTGCT-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 224343.
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 354 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.469_477delAGCAGCAGC	p.Ser157_Ser159del	conservative_inframe_deletion	Exon 2 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.178_186delAGCAGCAGC	p.Ser60_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.469_477delAGCAGCAGC	p.Ser157_Ser159del	conservative_inframe_deletion	Exon 2 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000566102.1	TSL:1	c.77-4201_77-4193delAGCAGCAGC		intron	N/A	ENSP00000455582.1	H3BQ32
	SALL1	ENST00000440970.6	TSL:5	c.469_477delAGCAGCAGC	p.Ser157_Ser159del	conservative_inframe_deletion	Exon 3 of 4	ENSP00000407914.2	Q9NSC2-1

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

GnomAD2 exomes AF: 0.00285 AC: 609 AN: 213596 AF XY: 0.00281

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 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

African (AFR) AF: 0.000825 AC: 27 AN: 32714

American (AMR) AF: 0.00216 AC: 94 AN: 43538

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 66 AN: 25464

East Asian (EAS) AF: 0.0000779 AC: 3 AN: 38530

South Asian (SAS) AF: 0.0000476 AC: 4 AN: 83980

European-Finnish (FIN) AF: 0.00160 AC: 83 AN: 51878

Middle Eastern (MID) AF: 0.000734 AC: 4 AN: 5450

European-Non Finnish (NFE) AF: 0.00443 AC: 4818 AN: 1088530

Other (OTH) AF: 0.00291 AC: 171 AN: 58816

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

African (AFR) AF: 0.000875 AC: 36 AN: 41142

American (AMR) AF: 0.00237 AC: 36 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4736

European-Finnish (FIN) AF: 0.00144 AC: 15 AN: 10450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00386 AC: 261 AN: 67694

Other (OTH) AF: 0.00190 AC: 4 AN: 2102

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00230

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	2	not specified (2)
-	-	1	Townes syndrome (1)
-	1	-	Townes-Brocks syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
Mutation Taster		=177/23	polymorphism

Splicing

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: COSV51758554; COSMIC: COSV51758554;