Variant 3-45595906-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014240.3(LIMD1):c.1027T>A(p.Ser343Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 1,614,166 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00052 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

LIMD1
NM_014240.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0380

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.018128216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMD1	NM_014240.3 linkuse as main transcript	c.1027T>A	p.Ser343Thr	missense_variant	1/8	ENST00000273317.5	NP_055055.1
LIMD1	XM_011534207.4 linkuse as main transcript	c.1027T>A	p.Ser343Thr	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.1027T>A	p.Ser343Thr	missense_variant	1/8	1	NM_014240.3	ENSP00000273317	P1
LIMD1	ENST00000440097.5 linkuse as main transcript	c.1027T>A	p.Ser343Thr	missense_variant	1/6	5		ENSP00000394537
LIMD1	ENST00000465039.5 linkuse as main transcript	n.102-16986T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000366

AC:

AN:

251476

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000668

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00105

AC:

1529

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

739

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.000519

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000912

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000745

Hom.:

Bravo

AF:

0.000484

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000371

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.000533

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

Jul 13, 2021

The c.1027T>A (p.S343T) alteration is located in exon 1 (coding exon 1) of the LIMD1 gene. This alteration results from a T to A substitution at nucleotide position 1027, causing the serine (S) at amino acid position 343 to be replaced by a threonine (T). 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

0.080

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.95

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.035

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.17

T;T

Polyphen

0.027

.;B

Vest4

0.081

MVP

0.38

MPC

0.11

ClinPred

0.015

GERP RS

0.87

Varity_R

0.22

gMVP

0.33

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