Variant 4-41360893-C-A 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.53C>A(p.Pro18Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LIMCH1
ENST00000313860.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.22

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=0.26768088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
LIMCH1	NM_001330787.2 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	1/27
LIMCH1	NM_014988.5 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	1/27
LIMCH1	NM_001330790.2 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	1/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
LIMCH1	ENST00000313860.12 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	1/27	1	P3	Q9UPQ0-1
LIMCH1	ENST00000512820.5 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	1/26	1		Q9UPQ0-4
LIMCH1	ENST00000512946.5 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	1/26	1	A1	Q9UPQ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1436702

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712724

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 21, 2024

The c.53C>A (p.P18Q) alteration is located in exon 1 (coding exon 1) of the LIMCH1 gene. This alteration results from a C to A substitution at nucleotide position 53, causing the proline (P) at amino acid position 18 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.0019

.;.;T;T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.80

T;T;T;T;T

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.90

L;L;L;.;L

MutationTaster

Benign

0.88

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

PROVEAN

Benign

-0.24

N;N;N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.017

D;D;D;D;D

Sift4G

Uncertain

0.025

D;D;D;D;D

Polyphen

1.0

.;D;D;D;D

Vest4

0.33

MutPred

0.39

Loss of glycosylation at P18 (P = 0.0035);Loss of glycosylation at P18 (P = 0.0035);Loss of glycosylation at P18 (P = 0.0035);Loss of glycosylation at P18 (P = 0.0035);Loss of glycosylation at P18 (P = 0.0035);

MVP

0.15

MPC

0.14

ClinPred

0.83

GERP RS

4.3

Varity_R

0.16

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over