chr3-45595450-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014240.3(LIMD1):​c.571G>A​(p.Gly191Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 ( 0 hom. )

Consequence

LIMD1
NM_014240.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.765
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0820348).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LIMD1NM_014240.3 linkuse as main transcriptc.571G>A p.Gly191Ser missense_variant 1/8 ENST00000273317.5 NP_055055.1
LIMD1XM_011534207.4 linkuse as main transcriptc.571G>A p.Gly191Ser 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.571G>A p.Gly191Ser missense_variant 1/81 NM_014240.3 ENSP00000273317 P1
LIMD1ENST00000440097.5 linkuse as main transcriptc.571G>A p.Gly191Ser missense_variant 1/65 ENSP00000394537
LIMD1ENST00000465039.5 linkuse as main transcriptn.102-17442G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461648
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727104
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

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 GeneticsMar 31, 2023The c.571G>A (p.G191S) 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 571, causing the glycine (G) at amino acid position 191 to be replaced by a serine (S). 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
0.073
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
14
DANN
Benign
0.97
DEOGEN2
Benign
0.12
.;T
Eigen
Benign
-0.97
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.60
T;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.082
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.69
.;N
MutationTaster
Benign
0.99
N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.094
Sift
Benign
0.046
D;D
Sift4G
Benign
0.29
T;T
Polyphen
0.011
.;B
Vest4
0.065
MutPred
0.15
Gain of phosphorylation at G191 (P = 0.0286);Gain of phosphorylation at G191 (P = 0.0286);
MVP
0.63
MPC
0.13
ClinPred
0.096
T
GERP RS
1.7
Varity_R
0.053
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-45636942; API