12-50177820-C-T

Variant names:

• chr12-50177820-C-T
• NM_016357.5:c.1524G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016357.5(LIMA1):​c.1524G>A​(p.Met508Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M508L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LIMA1 NM_016357.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32090685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMA1	NM_016357.5	c.1524G>A	p.Met508Ile	missense_variant	Exon 11 of 11	ENST00000341247.9	NP_057441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMA1	ENST00000341247.9	c.1524G>A	p.Met508Ile	missense_variant	Exon 11 of 11	1	NM_016357.5	ENSP00000340184.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461342 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726984

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1527G>A (p.M509I) alteration is located in exon 11 (coding exon 10) of the LIMA1 gene. This alteration results from a G to A substitution at nucleotide position 1527, causing the methionine (M) at amino acid position 509 to be replaced by an isoleucine (I). 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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T;.;.;.;T;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.32	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.9	.;.;.;.;M;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.058	T;D;T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T;T;T
Polyphen		0.99, 0.34	.;.;.;.;D;.;B
Vest4		0.39
MutPred		0.31		.;.;.;.;Gain of catalytic residue at V503 (P = 0.0103);.;.;
MVP		0.88
MPC		0.47
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50571603;