Variant 3-45595256-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014240.3(LIMD1):c.377C>T(p.Pro126Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,610,582 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

LIMD1
NM_014240.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.661

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057444572).

BP6

Variant 3-45595256-C-T is Benign according to our data. Variant chr3-45595256-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3118875.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMD1	NM_014240.3 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	1/8	ENST00000273317.5	NP_055055.1
LIMD1	XM_011534207.4 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	1/2		XP_011532509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LIMD1	ENST00000273317.5 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	1/8	1	NM_014240.3	ENSP00000273317	P1
LIMD1	ENST00000440097.5 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	1/6	5		ENSP00000394537
LIMD1	ENST00000465039.5 linkuse as main transcript	n.102-17636C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000176

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000183

AC:

AN:

246406

Hom.:

AF XY:

0.000142

AC XY:

AN XY:

133900

show subpopulations

Gnomad AFR exome

AF:

0.00159

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:

0.000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

337

AN:

1458274

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

148

AN XY:

725330

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000420

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.000453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.20

DANN

Benign

0.73

DEOGEN2

Benign

0.085

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.050

Sift

Benign

0.25

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

.;B

Vest4

0.031

MVP

0.25

MPC

0.12

ClinPred

0.016

GERP RS

-5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.068

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