17-18233890-ACC-TCG

Variant names:

• chr17-18233890-ACC-TCG
• NM_004140.4:c.505_507delACCinsTCG
• LLGL1 p.Thr169Ser

Variant summary

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

The NM_004140.4(LLGL1):​c.505_507delACCinsTCG​(p.Thr169Ser) variant causes a missense 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 MNV, 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T169A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LLGL1 NM_004140.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 0 publications found

Genes affected

LLGL1 (HGNC:6628): (LLGL scribble cell polarity complex component 1) This gene encodes a protein that is similar to a tumor suppressor in Drosophila. The protein is part of a cytoskeletal network and is associated with nonmuscle myosin II heavy chain and a kinase that specifically phosphorylates this protein at serine residues. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

LLGL1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004140.4. 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
	LLGL1	NM_004140.4	MANE Select	c.505_507delACCinsTCG	p.Thr169Ser	missense	N/A	NP_004131.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LLGL1	ENST00000316843.9	TSL:1 MANE Select	c.505_507delACCinsTCG	p.Thr169Ser	missense	N/A	ENSP00000321537.4	Q15334
	LLGL1	ENST00000855607.1		c.505_507delACCinsTCG	p.Thr169Ser	missense	N/A	ENSP00000525666.1
	LLGL1	ENST00000855606.1		c.505_507delACCinsTCG	p.Thr169Ser	missense	N/A	ENSP00000525665.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-18137204;