chr3-45594902-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014240.3(LIMD1):c.23G>A(p.Gly8Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,610,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
LIMD1
NM_014240.3 missense
NM_014240.3 missense
Scores
2
13
4
Clinical Significance
Conservation
PhyloP100: 9.57
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LIMD1 | NM_014240.3 | c.23G>A | p.Gly8Asp | missense_variant | 1/8 | ENST00000273317.5 | NP_055055.1 | |
LIMD1 | XM_011534207.4 | c.23G>A | p.Gly8Asp | missense_variant | 1/2 | XP_011532509.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LIMD1 | ENST00000273317.5 | c.23G>A | p.Gly8Asp | missense_variant | 1/8 | 1 | NM_014240.3 | ENSP00000273317 | P1 | |
LIMD1 | ENST00000440097.5 | c.23G>A | p.Gly8Asp | missense_variant | 1/6 | 5 | ENSP00000394537 | |||
LIMD1 | ENST00000465039.5 | n.102-17990G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151342Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250542Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135390
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1459446Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9AN XY: 725948
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151342Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2AN XY: 73934
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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 | Nov 08, 2022 | The c.23G>A (p.G8D) 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 23, causing the glycine (G) at amino acid position 8 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
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP
MPC
0.66
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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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