chr3-45595688-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014240.3(LIMD1):​c.809G>A​(p.Arg270Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

LIMD1
NM_014240.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.396
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 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
LIMD1NM_014240.3 linkuse as main transcriptc.809G>A p.Arg270Gln missense_variant 1/8 ENST00000273317.5 NP_055055.1
LIMD1XM_011534207.4 linkuse as main transcriptc.809G>A p.Arg270Gln 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.809G>A p.Arg270Gln missense_variant 1/81 NM_014240.3 ENSP00000273317 P1
LIMD1ENST00000440097.5 linkuse as main transcriptc.809G>A p.Arg270Gln missense_variant 1/65 ENSP00000394537
LIMD1ENST00000465039.5 linkuse as main transcriptn.102-17204G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251338
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461826
Hom.:
0
Cov.:
35
AF XY:
0.00000550
AC XY:
4
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152334
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
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 GeneticsMar 18, 2024The c.809G>A (p.R270Q) 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 809, causing the arginine (R) at amino acid position 270 to be replaced by a glutamine (Q). 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
0.076
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
.;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.064
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.8
.;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.89
N;N
REVEL
Benign
0.077
Sift
Uncertain
0.018
D;D
Sift4G
Benign
0.35
T;T
Polyphen
0.32
.;B
Vest4
0.20
MVP
0.57
MPC
0.41
ClinPred
0.19
T
GERP RS
2.9
Varity_R
0.075
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.23
Position offset: 1

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: rs201387403; hg19: chr3-45637180; API