Variant 3-45595469-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014240.3(LIMD1):c.590C>T(p.Ser197Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,613,796 control chromosomes in the GnomAD database, including 4 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 0.00093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

LIMD1
NM_014240.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.343

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004643023).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMD1	NM_014240.3 linkuse as main transcript	c.590C>T	p.Ser197Phe	missense_variant	1/8	ENST00000273317.5	NP_055055.1
LIMD1	XM_011534207.4 linkuse as main transcript	c.590C>T	p.Ser197Phe	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.590C>T	p.Ser197Phe	missense_variant	1/8	1	NM_014240.3	ENSP00000273317	P1
LIMD1	ENST00000440097.5 linkuse as main transcript	c.590C>T	p.Ser197Phe	missense_variant	1/6	5		ENSP00000394537
LIMD1	ENST00000465039.5 linkuse as main transcript	n.102-17423C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000926

AC:

141

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00110

AC:

275

AN:

250884

Hom.:

AF XY:

0.00105

AC XY:

142

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00449

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00146

AC:

2134

AN:

1461470

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1039

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00164

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.000926

AC:

141

AN:

152326

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00114

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000848

AC:

103

EpiCase

AF:

0.00185

EpiControl

AF:

0.00142

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

Dec 18, 2023

The c.590C>T (p.S197F) alteration is located in exon 1 (coding exon 1) of the LIMD1 gene. This alteration results from a C to T substitution at nucleotide position 590, causing the serine (S) at amino acid position 197 to be replaced by a phenylalanine (F). 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

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.7

DANN

Benign

0.54

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.034

Sift

Benign

0.24

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0

.;B

Vest4

0.11

MVP

0.30

MPC

0.13

ClinPred

0.0023

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.21

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