chr13-43881111-CTG-C

Position:

• chr13-43881111-CTG-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_153218.4(LACC1):​c.128_129del​(p.Cys43TyrfsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LACC1 NM_153218.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.50

Genes affected

LACC1 (HGNC:26789): (laccase domain containing 1) This gene encodes an oxidoreductase that promotes fatty-acid oxidation, with concomitant inflammasome activation, mitochondrial and NADPH-oxidase-dependent reactive oxygen species production, and bactericidal activity of macrophages. The encoded protein forms a complex with fatty acid synthase on peroxisomes and is thought to be modulated by peroxisome proliferator-activated receptor signaling events. Naturally occurring mutations in this gene are associated with inflammatory bowel disease, Behcet's disease, leprosy, ulcerative colitis, early-onset Crohn's disease, and systemic juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-43881111-CTG-C is Pathogenic according to our data. Variant chr13-43881111-CTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 814026.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACC1	NM_153218.4	c.128_129del	p.Cys43TyrfsTer6	frameshift_variant	2/7	ENST00000325686.7	NP_694950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACC1	ENST00000325686.7	c.128_129del	p.Cys43TyrfsTer6	frameshift_variant	2/7	1	NM_153218.4	ENSP00000317619	P1
LACC1	ENST00000425906.1	c.128_129del	p.Cys43TyrfsTer6	frameshift_variant	2/2	2		ENSP00000394179
LACC1	ENST00000441843.5	c.128_129del	p.Cys43TyrfsTer6	frameshift_variant	2/7	5		ENSP00000391747	P1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Juvenile arthritis due to defect in LACC1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1594883470; hg19: chr13-44455247;