16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCT

Variant names:

• chr16-51141744-C-CGCT
• rs113614842
• NM_002968.3:c.475_477dupAGC

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_002968.3(SALL1):​c.475_477dupAGC​(p.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 0.0219 in 1,579,498 control chromosomes in the GnomAD database, including 444 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (289 hom., cov: 31)
  • Exomes 𝑓: 0.020 (155 hom.)
• Consequence: SALL1 NM_002968.3 conservative_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.34
• 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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002968.3
• BP6: Variant 16-51141744-C-CGCT is Benign according to our data. Variant chr16-51141744-C-CGCT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

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_477dupAGC	p.Ser159dup	conservative_inframe_insertion	Exon 2 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.184_186dupAGC	p.Ser62dup	conservative_inframe_insertion	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_477dupAGC	p.Ser159dup	conservative_inframe_insertion	Exon 2 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000566102.1	TSL:1	c.77-4195_77-4193dupAGC		intron	N/A	ENSP00000455582.1	H3BQ32
	SALL1	ENST00000440970.6	TSL:5	c.475_477dupAGC	p.Ser159dup	conservative_inframe_insertion	Exon 3 of 4	ENSP00000407914.2	Q9NSC2-1

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6342 AN: 150958 Hom.: 284 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.00354

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0375

GnomAD2 exomes AF: 0.0240 AC: 5119 AN: 213596 AF XY: 0.0219

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.0182

Gnomad ASJ exome AF: 0.0305

Gnomad EAS exome AF: 0.0220

Gnomad FIN exome AF: 0.00468

Gnomad NFE exome AF: 0.0186

Gnomad OTH exome AF: 0.0207

GnomAD4 exome AF: 0.0198 AC: 28257 AN: 1428430 Hom.: 155 Cov.: 43 AF XY: 0.0192 AC XY: 13635 AN XY: 710460

African (AFR) AF: 0.108 AC: 3526 AN: 32666

American (AMR) AF: 0.0169 AC: 735 AN: 43528

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 755 AN: 25456

East Asian (EAS) AF: 0.0207 AC: 797 AN: 38524

South Asian (SAS) AF: 0.0172 AC: 1447 AN: 83966

European-Finnish (FIN) AF: 0.00407 AC: 211 AN: 51876

Middle Eastern (MID) AF: 0.0334 AC: 182 AN: 5450

European-Non Finnish (NFE) AF: 0.0175 AC: 19070 AN: 1088162

Other (OTH) AF: 0.0261 AC: 1534 AN: 58802

GnomAD4 genome AF: 0.0422 AC: 6368 AN: 151068 Hom.: 289 Cov.: 31 AF XY: 0.0403 AC XY: 2972 AN XY: 73796

African (AFR) AF: 0.109 AC: 4476 AN: 41106

American (AMR) AF: 0.0197 AC: 300 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 104 AN: 3448

East Asian (EAS) AF: 0.0190 AC: 97 AN: 5116

South Asian (SAS) AF: 0.0192 AC: 91 AN: 4736

European-Finnish (FIN) AF: 0.00354 AC: 37 AN: 10452

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0172 AC: 1161 AN: 67692

Other (OTH) AF: 0.0385 AC: 81 AN: 2102

Alfa AF: 0.0102 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Townes-Brocks syndrome 1 (4)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Townes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=81/19	polymorphism (auto)

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: COSV51755521; COSMIC: COSV51755521;