chr3-45595222-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014240.3(LIMD1):​c.343G>A​(p.Gly115Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000483 in 1,450,412 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

LIMD1
NM_014240.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67
Variant links:
Genes affected
LIMD1 (HGNC:6612): (LIM domain containing 1) Predicted to enable transcription corepressor activity. Involved in several processes, including negative regulation of hippo signaling; regulation of gene expression; and response to hypoxia. Acts upstream of or within P-body assembly and gene silencing by miRNA. Located in several cellular components, including P-body; adherens junction; and focal adhesion. Part of RISC complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.31093693).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LIMD1NM_014240.3 linkuse as main transcriptc.343G>A p.Gly115Arg missense_variant 1/8 ENST00000273317.5 NP_055055.1
LIMD1XM_011534207.4 linkuse as main transcriptc.343G>A p.Gly115Arg missense_variant 1/2 XP_011532509.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LIMD1ENST00000273317.5 linkuse as main transcriptc.343G>A p.Gly115Arg missense_variant 1/81 NM_014240.3 ENSP00000273317 P1
LIMD1ENST00000440097.5 linkuse as main transcriptc.343G>A p.Gly115Arg missense_variant 1/65 ENSP00000394537
LIMD1ENST00000465039.5 linkuse as main transcriptn.102-17670G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000829
AC:
2
AN:
241356
Hom.:
0
AF XY:
0.0000152
AC XY:
2
AN XY:
131312
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000183
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000483
AC:
7
AN:
1450412
Hom.:
0
Cov.:
35
AF XY:
0.00000833
AC XY:
6
AN XY:
720228
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:
0.00000633
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsFeb 06, 2024The c.343G>A (p.G115R) alteration is located in exon 1 (coding exon 1) of the LIMD1 gene. This alteration results from a G to A substitution at nucleotide position 343, causing the glycine (G) at amino acid position 115 to be replaced by an arginine (R). 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
0.16
BayesDel_addAF
Uncertain
0.024
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
.;T
Eigen
Benign
0.15
Eigen_PC
Benign
0.059
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Uncertain
2.4
.;M
MutationTaster
Benign
0.95
D;D
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Benign
0.24
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.030
D;D
Polyphen
0.99
.;D
Vest4
0.39
MutPred
0.30
Gain of methylation at G115 (P = 0.0312);Gain of methylation at G115 (P = 0.0312);
MVP
0.69
MPC
0.54
ClinPred
0.98
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.18
gMVP
0.28

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: rs764424744; hg19: chr3-45636714; API