13-43883789-ATC-GTG

Variant names:

• chr13-43883789-ATC-GTG
• NM_153218.4:c.760_762delATCinsGTG
• LACC1 p.Ile254Val

Variant summary

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

The NM_153218.4(LACC1):​c.760_762delATCinsGTG​(p.Ile254Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.0000497 in 14 alleles, including 0 homozygotes. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I254M) has been classified as Uncertain significance.

• Frequency: GnomAD MNV: 𝑓 0.000050 Genomes: not found (cov: 32)
• Consequence: LACC1 NM_153218.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.93
• Publications: 0 publications found

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]

LACC1 Gene-Disease associations (from GenCC):

• juvenile arthritis due to defect in LACC1

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000281883 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153218.4. 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
	LACC1	NM_153218.4	MANE Select	c.760_762delATCinsGTG	p.Ile254Val	missense	N/A	NP_694950.2	Q8IV20
	LACC1	NM_001128303.2		c.760_762delATCinsGTG	p.Ile254Val	missense	N/A	NP_001121775.1	Q8IV20
	LACC1	NM_001350638.2		c.760_762delATCinsGTG	p.Ile254Val	missense	N/A	NP_001337567.1	Q8IV20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACC1	ENST00000325686.7	TSL:1 MANE Select	c.760_762delATCinsGTG	p.Ile254Val	missense	N/A	ENSP00000317619.5	Q8IV20
	LACC1	ENST00000851305.1		c.829_831delATCinsGTG	p.Ile277Val	missense	N/A	ENSP00000521364.1
	LACC1	ENST00000962492.1		c.829_831delATCinsGTG	p.Ile277Val	missense	N/A	ENSP00000632551.1

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

GnomAD MNV AF: 0.0000497 AC: 14 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.9

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: chr13-44457925;