rs111848977

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_198271.5(LMOD3):c.426A>G(p.Glu142Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,558,882 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 15 hom., cov: 31)

Exomes 𝑓: 0.00067 ( 11 hom. )

Consequence

LMOD3
NM_198271.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.307

Publications

3 publications found

Variant links:

Genes affected

LMOD3 (HGNC:6649): (leiomodin 3) The protein encoded by this gene is a member of the leiomodin family of proteins. This protein contains three actin-binding domains, a tropomyosin domain, a leucine-rich repeat domain, and a Wiskott-Aldrich syndrome protein homology 2 domain (WH2). Localization of this protein to the pointed ends of thin filaments has been observed, and there is evidence that this protein acts as a catalyst of actin nucleation, and is important to the organization of sarcomeric thin filaments in skeletal muscles. Mutations in this gene have been associated as one cause of Nemaline myopathy, as other genes have also been linked to this disorder. Nemaline myopathy is a disorder characterized by nonprogressive generalized muscle weakness and protein inclusions (nemaline bodies) in skeletal myofibers. Patients with mutations in this gene often present with a severe congenital form of the disorder. [provided by RefSeq, Jan 2015]

LMOD3 Gene-Disease associations (from GenCC):

nemaline myopathy 10
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
typical nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
severe congenital nemaline myopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LMOD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-69119929-T-C is Benign according to our data. Variant chr3-69119929-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.307 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00758 (1154/152274) while in subpopulation AFR AF = 0.0257 (1069/41556). AF 95% confidence interval is 0.0244. There are 15 homozygotes in GnomAd4. There are 570 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMOD3	NM_198271.5 link	c.426A>G	p.Glu142Glu	synonymous_variant	Exon 2 of 3	ENST00000420581.7	NP_938012.2	Q0VAK6-1
LMOD3	NM_001304418.3 link	c.426A>G	p.Glu142Glu	synonymous_variant	Exon 3 of 4		NP_001291347.1	Q0VAK6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMOD3	ENST00000420581.7 link	c.426A>G	p.Glu142Glu	synonymous_variant	Exon 2 of 3	1	NM_198271.5	ENSP00000414670.3	Q0VAK6-1
LMOD3	ENST00000475434.1 link	c.426A>G	p.Glu142Glu	synonymous_variant	Exon 3 of 4	5		ENSP00000418645.1	Q0VAK6-1
LMOD3	ENST00000489031.5 link	c.426A>G	p.Glu142Glu	synonymous_variant	Exon 3 of 4	2		ENSP00000417210.1	Q0VAK6-1

Frequencies

GnomAD3 genomes

AF:

0.00755

AC:

1149

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00156

AC:

267

AN:

171080

AF XY:

0.00136

show subpopulations

Gnomad AFR exome

AF:

0.0238

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000584

Gnomad OTH exome

AF:

0.000848

GnomAD4 exome

AF:

0.000666

AC:

937

AN:

1406608

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

410

AN XY:

695082

show subpopulations

African (AFR)

AF:

0.0222

AC:

712

AN:

32058

American (AMR)

AF:

0.00193

AC:

AN:

36222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25240

East Asian (EAS)

AF:

0.00

AC:

AN:

36800

South Asian (SAS)

AF:

0.0000496

AC:

AN:

80624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50386

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

1081198

Other (OTH)

AF:

0.00190

AC:

111

AN:

58378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00758

AC:

1154

AN:

152274

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

570

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0257

AC:

1069

AN:

41556

American (AMR)

AF:

0.00412

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68014

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.00836

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 05, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nemaline myopathy 10

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.9

(source)

DANN

Benign

0.47

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over