Variant 4-41494552-G-A 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.113G>A(p.Ser38Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 0.0000021 ( 0 hom. )

Consequence

LIMCH1
ENST00000313860.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.67

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=0.1930564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
LIMCH1	NM_001330787.2 linkuse as main transcript	c.113G>A	p.Ser38Asn	missense_variant	2/27
LIMCH1	NM_014988.5 linkuse as main transcript	c.113G>A	p.Ser38Asn	missense_variant	2/27
LIMCH1	NM_001330790.2 linkuse as main transcript	c.113G>A	p.Ser38Asn	missense_variant	2/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
LIMCH1	ENST00000313860.12 linkuse as main transcript	c.113G>A	p.Ser38Asn	missense_variant	2/27	1	P3	Q9UPQ0-1
LIMCH1	ENST00000512820.5 linkuse as main transcript	c.113G>A	p.Ser38Asn	missense_variant	2/26	1		Q9UPQ0-4
LIMCH1	ENST00000512946.5 linkuse as main transcript	c.113G>A	p.Ser38Asn	missense_variant	2/26	1	A1	Q9UPQ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250806

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460900

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726664

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

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 28, 2024

The c.113G>A (p.S38N) alteration is located in exon 2 (coding exon 2) of the LIMCH1 gene. This alteration results from a G to A substitution at nucleotide position 113, causing the serine (S) at amino acid position 38 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Benign

0.96

Eigen

Benign

0.052

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.68

N;N;N;.;N

MutationTaster

Benign

0.72

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

PROVEAN

Benign

0.55

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.25

T;T;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.40, 0.61, 0.97

.;B;P;D;B

Vest4

0.54

MutPred

0.25

Loss of phosphorylation at S38 (P = 0.0631);Loss of phosphorylation at S38 (P = 0.0631);Loss of phosphorylation at S38 (P = 0.0631);Loss of phosphorylation at S38 (P = 0.0631);Loss of phosphorylation at S38 (P = 0.0631);

MVP

0.19

MPC

0.63

ClinPred

0.59

GERP RS

4.3

Varity_R

0.13

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