Variant chr3-45677052-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014240.3(LIMD1):c.2024A>G(p.His675Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,404 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LIMD1
NM_014240.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.365

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]

LIMD1 links:

LIMD1-AS1 (HGNC:44107): (LIMD1 antisense RNA 1)

LIMD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051693052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMD1	NM_014240.3 linkuse as main transcript	c.2024A>G	p.His675Arg	missense_variant	8/8	ENST00000273317.5	NP_055055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMD1	ENST00000273317.5 linkuse as main transcript	c.2024A>G	p.His675Arg	missense_variant	8/8	1	NM_014240.3	ENSP00000273317	P1
LIMD1-AS1	ENST00000658801.1 linkuse as main transcript	n.3824T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

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:

0.00000798

AC:

AN:

250606

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

May 18, 2023

The c.2024A>G (p.H675R) alteration is located in exon 8 (coding exon 8) of the LIMD1 gene. This alteration results from a A to G substitution at nucleotide position 2024, causing the histidine (H) at amino acid position 675 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

0.081

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.16

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.51

M_CAP

Benign

0.0061

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.87

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

REVEL

Benign

0.029

Sift

Benign

0.097

Sift4G

Benign

0.69

Polyphen

0.0020

Vest4

0.077

MutPred

0.44

Gain of MoRF binding (P = 0.0106);

MVP

0.48

MPC

0.15

ClinPred

0.048

GERP RS

-0.13

Varity_R

0.090

gMVP

0.35

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over