12-50177285-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016357.5(LIMA1):​c.2059G>A​(p.Asp687Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,614,082 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

LIMA1
NM_016357.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.761
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03537658).
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIMA1NM_016357.5 linkc.2059G>A p.Asp687Asn 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.2059G>A p.Asp687Asn missense_variant Exon 11 of 11 1 NM_016357.5 ENSP00000340184.4 Q9UHB6-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152230
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000159
AC:
40
AN:
251356
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000954
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.0000369
AC:
54
AN:
1461852
Hom.:
0
Cov.:
32
AF XY:
0.0000206
AC XY:
15
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000984
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152230
Hom.:
1
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000106
ExAC
AF:
0.000272
AC:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2062G>A (p.D688N) 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 2062, causing the aspartic acid (D) at amino acid position 688 to be replaced by an asparagine (N). 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
0.074
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.011
T;.;.;.;T;.;T
Eigen
Benign
-0.087
Eigen_PC
Benign
-0.060
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.72
T;T;T;T;T;T;T
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.035
T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Benign
2.0
.;.;.;.;M;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.31
N;N;N;N;N;N;N
REVEL
Benign
0.21
Sift
Benign
0.19
T;T;T;T;T;T;T
Sift4G
Benign
0.11
T;T;T;T;T;T;T
Polyphen
0.014, 0.12
.;.;.;.;B;.;B
Vest4
0.16
MutPred
0.16
.;.;.;.;Gain of relative solvent accessibility (P = 0.0479);.;.;
MVP
0.93
MPC
0.22
ClinPred
0.060
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.046
gMVP
0.15

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: rs771373810; hg19: chr12-50571068; COSMIC: COSV57963636; COSMIC: COSV57963636; API