rs139192915

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_198271.5(LMOD3):c.39_41delTCT(p.Leu14del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,610,784 control chromosomes in the GnomAD database, including 615 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 49 hom., cov: 32)

Exomes 𝑓: 0.026 ( 566 hom. )

Consequence

LMOD3
NM_198271.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.01

Publications

4 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 -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_198271.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 3-69122345-GAGA-G is Benign according to our data. Variant chr3-69122345-GAGA-G is described in ClinVar as Benign. ClinVar VariationId is 475320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0169 (2570/152052) while in subpopulation NFE AF = 0.0285 (1934/67976). AF 95% confidence interval is 0.0274. There are 49 homozygotes in GnomAd4. There are 1207 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMOD3	NM_198271.5 link	c.39_41delTCT	p.Leu14del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000420581.7	NP_938012.2	Q0VAK6-1
LMOD3	NM_001304418.3 link	c.39_41delTCT	p.Leu14del	disruptive_inframe_deletion	Exon 2 of 4		NP_001291347.1	Q0VAK6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMOD3	ENST00000420581.7 link	c.39_41delTCT	p.Leu14del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_198271.5	ENSP00000414670.3	Q0VAK6-1
LMOD3	ENST00000475434.1 link	c.39_41delTCT	p.Leu14del	disruptive_inframe_deletion	Exon 2 of 4	5		ENSP00000418645.1	Q0VAK6-1
LMOD3	ENST00000489031.5 link	c.39_41delTCT	p.Leu14del	disruptive_inframe_deletion	Exon 2 of 4	2		ENSP00000417210.1	Q0VAK6-1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2571

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0187

Gnomad FIN

AF:

0.0100

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0284

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.0186

AC:

4579

AN:

246090

AF XY:

0.0194

show subpopulations

Gnomad AFR exome

AF:

0.00505

Gnomad AMR exome

AF:

0.00892

Gnomad ASJ exome

AF:

0.00793

Gnomad EAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.0272

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.0260

AC:

37904

AN:

1458732

Hom.:

566

AF XY:

0.0260

AC XY:

18868

AN XY:

725650

show subpopulations

African (AFR)

AF:

0.00427

AC:

143

AN:

33452

American (AMR)

AF:

0.00915

AC:

408

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00744

AC:

194

AN:

26086

East Asian (EAS)

AF:

0.00154

AC:

AN:

39608

South Asian (SAS)

AF:

0.0236

AC:

2035

AN:

86066

European-Finnish (FIN)

AF:

0.0142

AC:

756

AN:

53288

Middle Eastern (MID)

AF:

0.0247

AC:

142

AN:

5760

European-Non Finnish (NFE)

AF:

0.0296

AC:

32800

AN:

1109620

Other (OTH)

AF:

0.0227

AC:

1365

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

1605

3210

4816

6421

8026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1242

2484

3726

4968

6210

<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:

0.0169

AC:

2570

AN:

152052

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1207

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00487

AC:

202

AN:

41478

American (AMR)

AF:

0.0101

AC:

155

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3470

East Asian (EAS)

AF:

0.00309

AC:

AN:

5180

South Asian (SAS)

AF:

0.0185

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.0100

AC:

106

AN:

10554

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0285

AC:

1934

AN:

67976

Other (OTH)

AF:

0.0157

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

129

258

386

515

644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0209

Hom.:

Bravo

AF:

0.0164

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nemaline myopathy 10

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 06, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=86/14

polymorphism (auto)

(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