Variant 4-41494593-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000313860.12(LIMCH1):c.154A>G(p.Ile52Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,458,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

LIMCH1
ENST00000313860.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.24

Variant links:

Genes affected

LIMCH1 (HGNC:29191): (LIM and calponin homology domains 1) Enables myosin II head/neck binding activity. Involved in several processes, including cytoplasmic actin-based contraction involved in cell motility; positive regulation of stress fiber assembly; and regulation of focal adhesion assembly. Located in stress fiber. Colocalizes with myosin II complex. [provided by Alliance of Genome Resources, Apr 2022]

LIMCH1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39309227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
LIMCH1	NM_001330787.2 linkuse as main transcript	c.154A>G	p.Ile52Val	missense_variant	2/27
LIMCH1	NM_014988.5 linkuse as main transcript	c.154A>G	p.Ile52Val	missense_variant	2/27
LIMCH1	NM_001330790.2 linkuse as main transcript	c.154A>G	p.Ile52Val	missense_variant	2/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
LIMCH1	ENST00000313860.12 linkuse as main transcript	c.154A>G	p.Ile52Val	missense_variant	2/27	1	P3	Q9UPQ0-1
LIMCH1	ENST00000512820.5 linkuse as main transcript	c.154A>G	p.Ile52Val	missense_variant	2/26	1		Q9UPQ0-4
LIMCH1	ENST00000512946.5 linkuse as main transcript	c.154A>G	p.Ile52Val	missense_variant	2/26	1	A1	Q9UPQ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250456

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135342

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000234

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458612

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725678

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000135

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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

Jan 04, 2022

The c.154A>G (p.I52V) alteration is located in exon 2 (coding exon 2) of the LIMCH1 gene. This alteration results from a A to G substitution at nucleotide position 154, causing the isoleucine (I) at amino acid position 52 to be replaced by a valine (V). 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

0.21

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

0.098

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

N;N;N;.;N

MutationTaster

Benign

0.96

D;D;D;D;D;D;D

PROVEAN

Benign

0.080

N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.73

T;T;T;T;T

Sift4G

Benign

0.41

T;T;T;T;T

Polyphen

0.88, 0.90, 0.24

.;P;P;B;P

Vest4

0.69

MutPred

0.67

Loss of catalytic residue at L57 (P = 0.0419);Loss of catalytic residue at L57 (P = 0.0419);Loss of catalytic residue at L57 (P = 0.0419);Loss of catalytic residue at L57 (P = 0.0419);Loss of catalytic residue at L57 (P = 0.0419);

MVP

0.60

MPC

0.57

ClinPred

0.20

GERP RS

5.1

Varity_R

0.093

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