rs1555205375

Variant names:

• chr12-50200825-ATTCTCCTT-A
• rs1555205375
• NM_016357.5:c.916_923delAAGGAGAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016357.5(LIMA1):​c.916_923delAAGGAGAA​(p.Lys306CysfsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as association (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIMA1 NM_016357.5 frameshift
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 4.69
• Publications: 0 publications found

Genes affected

LIMA1 (HGNC:24636): (LIM domain and actin binding 1) This gene encodes a cytoskeleton-associated protein that inhibits actin filament depolymerization and cross-links filaments in bundles. It is downregulated in some cancer cell lines. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, and expression of some of the variants maybe independently regulated. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016357.5. 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
	LIMA1	NM_016357.5	MANE Select	c.916_923delAAGGAGAA	p.Lys306CysfsTer6	frameshift	Exon 7 of 11	NP_057441.1
	LIMA1	NM_001113546.2		c.916_923delAAGGAGAA	p.Lys306CysfsTer6	frameshift	Exon 7 of 11	NP_001107018.1
	LIMA1	NM_001394886.1		c.916_923delAAGGAGAA	p.Lys306CysfsTer6	frameshift	Exon 7 of 11	NP_001381815.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMA1	ENST00000341247.9	TSL:1 MANE Select	c.916_923delAAGGAGAA	p.Lys306CysfsTer6	frameshift	Exon 7 of 11	ENSP00000340184.4
	LIMA1	ENST00000394943.7	TSL:1	c.916_923delAAGGAGAA	p.Lys306CysfsTer6	frameshift	Exon 7 of 11	ENSP00000378400.3
	LIMA1	ENST00000552783.5	TSL:1	c.436_443delAAGGAGAA	p.Lys146CysfsTer6	frameshift	Exon 4 of 8	ENSP00000448779.1

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

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs1555205375; hg19: chr12-50594608;