13-43880988-G-A

Variant summary

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

The NM_153218.4(LACC1):c.3G>A(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LACC1 NM_153218.4 start_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.23

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: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-43880988-G-A is Pathogenic according to our data. Variant chr13-43880988-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 814023.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LACC1	NM_153218.4	c.3G>A	p.Met1?	start_lost	2/7	ENST00000325686.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LACC1	ENST00000325686.7	c.3G>A	p.Met1?	start_lost	2/7	1	NM_153218.4	P1
LACC1	ENST00000441843.5	c.3G>A	p.Met1?	start_lost	2/7	5		P1
LACC1	ENST00000425906.1	c.3G>A	p.Met1?	start_lost	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Feb 29, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.082	T;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;.
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;D
PROVEAN	Benign	-1.3	N;D;N
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.92	P;.;P
Vest4		0.90
MutPred		0.97		Gain of catalytic residue at M1 (P = 0.0223);Gain of catalytic residue at M1 (P = 0.0223);Gain of catalytic residue at M1 (P = 0.0223);
MVP		0.72
ClinPred		0.98	D
GERP RS		6.1
Varity_R		0.78
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1594882933; hg19: chr13-44455124;