chr12-50177296-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_016357.5(LIMA1):c.2048G>A(p.Gly683Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,614,162 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 1 hom. )
Consequence
LIMA1
NM_016357.5 missense
NM_016357.5 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 1.15
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04559636).
BS2
?
High AC in GnomAd at 33 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIMA1 | NM_016357.5 | c.2048G>A | p.Gly683Asp | missense_variant | 11/11 | ENST00000341247.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIMA1 | ENST00000341247.9 | c.2048G>A | p.Gly683Asp | missense_variant | 11/11 | 1 | NM_016357.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152200Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000362 AC: 91AN: 251404Hom.: 0 AF XY: 0.000456 AC XY: 62AN XY: 135870
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GnomAD4 exome AF: 0.000271 AC: 396AN: 1461844Hom.: 1 Cov.: 32 AF XY: 0.000322 AC XY: 234AN XY: 727214
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GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74490
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2023 | The c.2051G>A (p.G684D) 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 2051, causing the glycine (G) at amino acid position 684 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
1.0, 0.82
.;.;.;.;D;.;P
Vest4
MVP
MPC
0.36
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at