NM_002968.3:c.76+32_76+37delACACAC

Variant names:

• chr16-51151128-CGTGTGT-C
• rs200502187
• NM_002968.3:c.76+32_76+37delACACAC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002968.3(SALL1):​c.76+32_76+37delACACAC variant causes a intron change. The variant allele was found at a frequency of 0.0000015 in 1,332,776 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SALL1 NM_002968.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.59
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Townes-Brocks syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285367 (HGNC:58539):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.76+32_76+37delACACAC		intron	N/A	NP_002959.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.76+32_76+37delACACAC		intron	N/A	ENSP00000251020.4
	SALL1	ENST00000566102.1	TSL:1	c.76+32_76+37delACACAC		intron	N/A	ENSP00000455582.1
	SALL1	ENST00000440970.6	TSL:5	c.76+32_76+37delACACAC		intron	N/A	ENSP00000407914.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1332776 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 663790

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30728

American (AMR) AF: 0.00 AC: 0 AN: 37442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24470

East Asian (EAS) AF: 0.00 AC: 0 AN: 36700

South Asian (SAS) AF: 0.00 AC: 0 AN: 76448

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: 0.00000195 AC: 2 AN: 1024008

Other (OTH) AF: 0.00 AC: 0 AN: 55798

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200502187; hg19: chr16-51185039;