12-50177709-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016357.5(LIMA1):​c.1635G>C​(p.Leu545Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,460,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

LIMA1
NM_016357.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.106
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16621259).
BS2
High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIMA1NM_016357.5 linkc.1635G>C p.Leu545Phe missense_variant Exon 11 of 11 ENST00000341247.9 NP_057441.1 Q9UHB6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIMA1ENST00000341247.9 linkc.1635G>C p.Leu545Phe missense_variant Exon 11 of 11 1 NM_016357.5 ENSP00000340184.4 Q9UHB6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1460378
Hom.:
0
Cov.:
32
AF XY:
0.0000165
AC XY:
12
AN XY:
726482
show subpopulations
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:
0.0000252
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1638G>C (p.L546F) alteration is located in exon 11 (coding exon 10) of the LIMA1 gene. This alteration results from a G to C substitution at nucleotide position 1638, causing the leucine (L) at amino acid position 546 to be replaced by a phenylalanine (F). 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
Benign
0.099
BayesDel_addAF
Benign
-0.029
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.025
T;.;.;.;T;.;T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.19
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.64
T;T;T;T;T;T;T
M_CAP
Benign
0.083
D
MetaRNN
Benign
0.17
T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Uncertain
2.6
.;.;.;.;M;.;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.6
N;N;N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.30
T;T;T;T;T;T;T
Sift4G
Benign
0.72
T;T;T;T;T;T;T
Polyphen
0.95, 0.17
.;.;.;.;P;.;B
Vest4
0.14
MutPred
0.21
.;.;.;.;Gain of helix (P = 0.0349);.;.;
MVP
0.90
MPC
0.30
ClinPred
0.12
T
GERP RS
1.9
Varity_R
0.057
gMVP
0.11

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1487733202; hg19: chr12-50571492; API