Variant 4-41360899-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000313860.12(LIMCH1):c.59C>G(p.Pro20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000765 in 1,437,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 0.0000077 ( 0 hom. )

Consequence

LIMCH1
ENST00000313860.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13742277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
LIMCH1	NM_001330787.2 linkuse as main transcript	c.59C>G	p.Pro20Arg	missense_variant	1/27
LIMCH1	NM_014988.5 linkuse as main transcript	c.59C>G	p.Pro20Arg	missense_variant	1/27
LIMCH1	NM_001330790.2 linkuse as main transcript	c.59C>G	p.Pro20Arg	missense_variant	1/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
LIMCH1	ENST00000313860.12 linkuse as main transcript	c.59C>G	p.Pro20Arg	missense_variant	1/27	1	P3	Q9UPQ0-1
LIMCH1	ENST00000512820.5 linkuse as main transcript	c.59C>G	p.Pro20Arg	missense_variant	1/26	1		Q9UPQ0-4
LIMCH1	ENST00000512946.5 linkuse as main transcript	c.59C>G	p.Pro20Arg	missense_variant	1/26	1	A1	Q9UPQ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000765

AC:

AN:

1437182

Hom.:

Cov.:

AF XY:

0.00000561

AC XY:

AN XY:

712954

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000725

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

Jun 21, 2022

The c.59C>G (p.P20R) alteration is located in exon 1 (coding exon 1) of the LIMCH1 gene. This alteration results from a C to G substitution at nucleotide position 59, causing the proline (P) at amino acid position 20 to be replaced by an arginine (R). 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

0.18

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0016

.;.;T;T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.83

T;T;T;T;T

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L;.;L

MutationTaster

Benign

0.69

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

PROVEAN

Benign

-1.3

N;N;N;N;N

REVEL

Benign

0.058

Sift

Benign

0.052

T;T;D;T;T

Sift4G

Uncertain

0.019

D;D;D;D;D

Polyphen

0.34, 0.23

.;B;B;B;B

Vest4

0.26

MutPred

0.28

Loss of glycosylation at P20 (P = 0.0016);Loss of glycosylation at P20 (P = 0.0016);Loss of glycosylation at P20 (P = 0.0016);Loss of glycosylation at P20 (P = 0.0016);Loss of glycosylation at P20 (P = 0.0016);

MVP

0.12

MPC

0.16

ClinPred

0.48

GERP RS

2.5

Varity_R

0.046

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