17-18233920-G-T

Position:

• chr17-18233920-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004140.4(LLGL1):​c.535G>T​(p.Gly179Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LLGL1 NM_004140.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24658632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LLGL1	NM_004140.4	c.535G>T	p.Gly179Cys	missense_variant	5/23	ENST00000316843.9	NP_004131.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LLGL1	ENST00000316843.9	c.535G>T	p.Gly179Cys	missense_variant	5/23	1	NM_004140.4	ENSP00000321537.4
LLGL1	ENST00000479155.1	n.19G>T		non_coding_transcript_exon_variant	1/15	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.535G>T (p.G179C) alteration is located in exon 5 (coding exon 5) of the LLGL1 gene. This alteration results from a G to T substitution at nucleotide position 535, causing the glycine (G) at amino acid position 179 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;.
Eigen	Benign	0.039
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.74	P;.
Vest4		0.28
MutPred		0.49		Gain of catalytic residue at P178 (P = 0.0135);Gain of catalytic residue at P178 (P = 0.0135);
MVP		0.11
MPC		0.33
ClinPred		0.62	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.30
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18137234;