Variant 4-41494537-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000313860.12(LIMCH1):c.98A>G(p.Gln33Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,458,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LIMCH1
ENST00000313860.12 missense, splice_region

Scores

Splicing: ADA: 0.8110

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.36

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
LIMCH1	NM_001330787.2 linkuse as main transcript	c.98A>G	p.Gln33Arg	missense_variant, splice_region_variant	2/27
LIMCH1	NM_014988.5 linkuse as main transcript	c.98A>G	p.Gln33Arg	missense_variant, splice_region_variant	2/27
LIMCH1	NM_001330790.2 linkuse as main transcript	c.98A>G	p.Gln33Arg	missense_variant, splice_region_variant	2/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
LIMCH1	ENST00000313860.12 linkuse as main transcript	c.98A>G	p.Gln33Arg	missense_variant, splice_region_variant	2/27	1	P3	Q9UPQ0-1
LIMCH1	ENST00000512820.5 linkuse as main transcript	c.98A>G	p.Gln33Arg	missense_variant, splice_region_variant	2/26	1		Q9UPQ0-4
LIMCH1	ENST00000512946.5 linkuse as main transcript	c.98A>G	p.Gln33Arg	missense_variant, splice_region_variant	2/26	1	A1	Q9UPQ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247750

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000550

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:

0.00000137

AC:

AN:

1458048

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725020

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:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;D;D;D;T

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.48

T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.71

N;N;N;.;N

MutationTaster

Benign

0.60

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

PROVEAN

Benign

-0.74

N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.14

T;T;T;T;T

Sift4G

Uncertain

0.028

D;D;D;D;D

Polyphen

0.98, 0.98, 0.99

.;D;D;D;D

Vest4

0.68

MutPred

0.45

Gain of MoRF binding (P = 0.0162);Gain of MoRF binding (P = 0.0162);Gain of MoRF binding (P = 0.0162);Gain of MoRF binding (P = 0.0162);Gain of MoRF binding (P = 0.0162);

MVP

0.31

MPC

0.68

ClinPred

0.68

GERP RS

5.1

Varity_R

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.81

dbscSNV1_RF

Benign

0.68

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over