16-51137582-CAGAG-CAG

Variant names:

• chr16-51137582-CAG-C
• rs142249003
• NM_002968.3:c.3535-32_3535-31delCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002968.3(SALL1):​c.3535-32_3535-31delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 1,368,248 control chromosomes in the GnomAD database, including 1,093 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (104 hom., cov: 31)
  • Exomes 𝑓: 0.056 (989 hom.)
• Consequence: SALL1 NM_002968.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.239
• Publications: 1 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Townes-Brocks syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-51137582-CAG-C is Benign according to our data. Variant chr16-51137582-CAG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.062 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.3535-32_3535-31delCT		intron	N/A	NP_002959.2
	SALL1	NM_001127892.2		c.3244-32_3244-31delCT		intron	N/A	NP_001121364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.3535-32_3535-31delCT		intron	N/A	ENSP00000251020.4
	SALL1	ENST00000566102.1	TSL:1	c.77-32_77-31delCT		intron	N/A	ENSP00000455582.1
	SALL1	ENST00000440970.6	TSL:5	c.3535-32_3535-31delCT		intron	N/A	ENSP00000407914.2

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4788 AN: 150082 Hom.: 104 Cov.: 31

Gnomad AFR AF: 0.00682

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0273

Gnomad EAS AF: 0.00175

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.0347

GnomAD2 exomes AF: 0.0808 AC: 12617 AN: 156212 AF XY: 0.0850

Gnomad AFR exome AF: 0.0317

Gnomad AMR exome AF: 0.0723

Gnomad ASJ exome AF: 0.0843

Gnomad EAS exome AF: 0.0183

Gnomad FIN exome AF: 0.0956

Gnomad NFE exome AF: 0.0910

Gnomad OTH exome AF: 0.0755

GnomAD4 exome AF: 0.0555 AC: 67607 AN: 1218058 Hom.: 989 AF XY: 0.0564 AC XY: 34198 AN XY: 605994

African (AFR) AF: 0.0196 AC: 541 AN: 27604

American (AMR) AF: 0.0541 AC: 2007 AN: 37072

Ashkenazi Jewish (ASJ) AF: 0.0495 AC: 1081 AN: 21846

East Asian (EAS) AF: 0.00724 AC: 229 AN: 31644

South Asian (SAS) AF: 0.0636 AC: 4239 AN: 66600

European-Finnish (FIN) AF: 0.0709 AC: 3037 AN: 42852

Middle Eastern (MID) AF: 0.0620 AC: 316 AN: 5100

European-Non Finnish (NFE) AF: 0.0573 AC: 53578 AN: 935558

Other (OTH) AF: 0.0518 AC: 2579 AN: 49782

GnomAD4 genome AF: 0.0319 AC: 4787 AN: 150190 Hom.: 104 Cov.: 31 AF XY: 0.0324 AC XY: 2378 AN XY: 73306

African (AFR) AF: 0.00680 AC: 279 AN: 41016

American (AMR) AF: 0.0313 AC: 472 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.0273 AC: 94 AN: 3442

East Asian (EAS) AF: 0.00176 AC: 9 AN: 5120

South Asian (SAS) AF: 0.0362 AC: 171 AN: 4728

European-Finnish (FIN) AF: 0.0652 AC: 656 AN: 10068

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0444 AC: 2994 AN: 67466

Other (OTH) AF: 0.0344 AC: 71 AN: 2066

Alfa AF: 0.0546 Hom.: 8

Bravo AF: 0.0281

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Aug 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs142249003; hg19: chr16-51171493; COSMIC: COSV51760863;