chr3-69119713-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_198271.5(LMOD3):c.642G>A(p.Ser214Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,613,790 control chromosomes in the GnomAD database, including 2,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S214S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.048 ( 507 hom., cov: 31)

Exomes 𝑓: 0.019 ( 2212 hom. )

Consequence

LMOD3
NM_198271.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.119

Publications

7 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 3-69119713-C-T is Benign according to our data. Variant chr3-69119713-C-T is described in ClinVar as Benign. ClinVar VariationId is 475330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.119 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMOD3	NM_198271.5 link	c.642G>A	p.Ser214Ser	synonymous_variant	Exon 2 of 3	ENST00000420581.7	NP_938012.2	Q0VAK6-1
LMOD3	NM_001304418.3 link	c.642G>A	p.Ser214Ser	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.642G>A	p.Ser214Ser	synonymous_variant	Exon 2 of 3	1	NM_198271.5	ENSP00000414670.3	Q0VAK6-1
LMOD3	ENST00000475434.1 link	c.642G>A	p.Ser214Ser	synonymous_variant	Exon 3 of 4	5		ENSP00000418645.1	Q0VAK6-1
LMOD3	ENST00000489031.5 link	c.642G>A	p.Ser214Ser	synonymous_variant	Exon 3 of 4	2		ENSP00000417210.1	Q0VAK6-1

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7258

AN:

152014

Hom.:

500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.0326

GnomAD2 exomes

AF:

0.0447

AC:

11144

AN:

249044

AF XY:

0.0457

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.000796

Gnomad EAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.00232

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0188

AC:

27503

AN:

1461658

Hom.:

2212

Cov.:

AF XY:

0.0214

AC XY:

15568

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.127

AC:

4238

AN:

33480

American (AMR)

AF:

0.0190

AC:

851

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000689

AC:

AN:

26134

East Asian (EAS)

AF:

0.229

AC:

9074

AN:

39690

South Asian (SAS)

AF:

0.124

AC:

10691

AN:

86254

European-Finnish (FIN)

AF:

0.00272

AC:

145

AN:

53384

Middle Eastern (MID)

AF:

0.0135

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000646

AC:

718

AN:

1111852

Other (OTH)

AF:

0.0280

AC:

1690

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1564

3129

4693

6258

7822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.0478

AC:

7275

AN:

152132

Hom.:

507

Cov.:

AF XY:

0.0505

AC XY:

3755

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.121

AC:

5037

AN:

41472

American (AMR)

AF:

0.0166

AC:

254

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.225

AC:

1162

AN:

5166

South Asian (SAS)

AF:

0.133

AC:

638

AN:

4808

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00138

AC:

AN:

68016

Other (OTH)

AF:

0.0322

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

316

632

947

1263

1579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0125

Hom.:

Bravo

AF:

0.0522

Asia WGS

AF:

0.137

AC:

475

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00107

ClinVar

Significance: 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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.5

(source)

DANN

Benign

0.60

PhyloP100

-0.12

Mutation Taster

=100/0

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

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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