Variant 4-41646544-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330672.2(LIMCH1):c.2471C>T(p.Ala824Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LIMCH1
NM_001330672.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMCH1	NM_001330672.2 linkuse as main transcript	c.2471C>T	p.Ala824Val	missense_variant	17/32	ENST00000503057.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMCH1	ENST00000503057.6 linkuse as main transcript	c.2471C>T	p.Ala824Val	missense_variant	17/32	1	NM_001330672.2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251472

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135904

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

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

Oct 10, 2023

The c.1316C>T (p.A439V) alteration is located in exon 12 (coding exon 12) of the LIMCH1 gene. This alteration results from a C to T substitution at nucleotide position 1316, causing the alanine (A) at amino acid position 439 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

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

.;.;.;T;T;.;T;.;T;T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.44

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.5

.;M;M;M;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.7

N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0050

D;D;D;D;D;D;T;D;D;D;D;D

Sift4G

Benign

0.23

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;.;D;D;D;D;D;.;.;D;D;D

Vest4

0.79

MutPred

0.22

.;.;.;.;.;.;Gain of glycosylation at S820 (P = 0.0058);.;.;.;.;.;

MVP

0.16

MPC

0.66

ClinPred

0.88

GERP RS

5.9

Varity_R

0.37

gMVP

0.60

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