chr16-51141744-C-CGCCGCCGCTGCT

Variant names:

• chr16-51141744-C-CGCCGCCGCTGCT
• rs1555475415
• NM_002968.3:c.477_478insAGCAGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The ENST00000251020.9(SALL1):​c.477_478insAGCAGCGGCGGC​(p.Ser159_Gly160insSerSerGlyGly) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SALL1 ENST00000251020.9 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000251020.9

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000251020.9. 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.477_478insAGCAGCGGCGGC	p.Ser159_Gly160insSerSerGlyGly	conservative_inframe_insertion	Exon 2 of 3	NP_002959.2
	SALL1	NM_001127892.2		c.186_187insAGCAGCGGCGGC	p.Ser62_Gly63insSerSerGlyGly	conservative_inframe_insertion	Exon 2 of 3	NP_001121364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.477_478insAGCAGCGGCGGC	p.Ser159_Gly160insSerSerGlyGly	conservative_inframe_insertion	Exon 2 of 3	ENSP00000251020.4
	SALL1	ENST00000566102.1	TSL:1	c.77-4193_77-4192insAGCAGCGGCGGC		intron	N/A	ENSP00000455582.1
	SALL1	ENST00000440970.6	TSL:5	c.477_478insAGCAGCGGCGGC	p.Ser159_Gly160insSerSerGlyGly	conservative_inframe_insertion	Exon 3 of 4	ENSP00000407914.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs1555475415; hg19: chr16-51175655;