Variant chr3-45595622-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014240.3(LIMD1):c.743A>G(p.Asn248Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,502 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LIMD1
NM_014240.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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 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=0.06932852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMD1	NM_014240.3 linkuse as main transcript	c.743A>G	p.Asn248Ser	missense_variant	1/8	ENST00000273317.5	NP_055055.1
LIMD1	XM_011534207.4 linkuse as main transcript	c.743A>G	p.Asn248Ser	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.743A>G	p.Asn248Ser	missense_variant	1/8	1	NM_014240.3	ENSP00000273317	P1
LIMD1	ENST00000440097.5 linkuse as main transcript	c.743A>G	p.Asn248Ser	missense_variant	1/6	5		ENSP00000394537
LIMD1	ENST00000465039.5 linkuse as main transcript	n.102-17270A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251300

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461784

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151718

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.0000484

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:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jan 16, 2024

The c.743A>G (p.N248S) alteration is located in exon 1 (coding exon 1) of the LIMD1 gene. This alteration results from a A to G substitution at nucleotide position 743, causing the asparagine (N) at amino acid position 248 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

0.085

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.097

.;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.013

D;D

Sift4G

Benign

0.66

T;T

Polyphen

0.0020

.;B

Vest4

0.12

MVP

0.52

MPC

0.097

ClinPred

0.054

GERP RS

4.7

Varity_R

0.10

gMVP

0.087

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