16-51151128-CGTGTGT-CGT

Variant names:

• chr16-51151128-CGTGT-C
• rs200502187
• NM_002968.3:c.76+34_76+37delACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002968.3(SALL1):​c.76+34_76+37delACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,484,592 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: SALL1 NM_002968.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• Publications: 0 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

ENSG00000285367 (HGNC:58539):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000555 (74/1332714) while in subpopulation AMR AF = 0.000107 (4/37442). AF 95% confidence interval is 0.0000359. There are 0 homozygotes in GnomAdExome4. There are 35 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High AC in GnomAd4 at 8 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.76+34_76+37delACAC		intron	N/A	NP_002959.2	Q9NSC2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.76+34_76+37delACAC		intron	N/A	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000566102.1	TSL:1	c.76+34_76+37delACAC		intron	N/A	ENSP00000455582.1	H3BQ32
	SALL1	ENST00000440970.6	TSL:5	c.76+34_76+37delACAC		intron	N/A	ENSP00000407914.2	Q9NSC2-1

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151878 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000105 AC: 17 AN: 161520 AF XY: 0.0000920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000428

Gnomad ASJ exome AF: 0.000872

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000109

Gnomad OTH exome AF: 0.000243

GnomAD4 exome AF: 0.0000555 AC: 74 AN: 1332714 Hom.: 0 AF XY: 0.0000527 AC XY: 35 AN XY: 663758

African (AFR) AF: 0.0000326 AC: 1 AN: 30720

American (AMR) AF: 0.000107 AC: 4 AN: 37442

Ashkenazi Jewish (ASJ) AF: 0.00110 AC: 27 AN: 24470

East Asian (EAS) AF: 0.00 AC: 0 AN: 36694

South Asian (SAS) AF: 0.0000262 AC: 2 AN: 76442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3924

European-Non Finnish (NFE) AF: 0.0000254 AC: 26 AN: 1023970

Other (OTH) AF: 0.000251 AC: 14 AN: 55794

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151878 Hom.: 0 Cov.: 32 AF XY: 0.0000809 AC XY: 6 AN XY: 74160

African (AFR) AF: 0.0000242 AC: 1 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67910

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000187 Hom.: 11

Bravo AF: 0.0000453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200502187; hg19: chr16-51185039;