3-69118837-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_198271.5(LMOD3):c.1518C>A(p.Pro506Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,608,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

LMOD3
NM_198271.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.08

Publications

0 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-69118837-G-T is Benign according to our data. Variant chr3-69118837-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 542088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.08 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198271.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMOD3	NM_198271.5	MANE Select	c.1518C>A	p.Pro506Pro	synonymous	Exon 2 of 3	NP_938012.2
	LMOD3	NM_001304418.3		c.1518C>A	p.Pro506Pro	synonymous	Exon 3 of 4	NP_001291347.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LMOD3	ENST00000420581.7	TSL:1 MANE Select	c.1518C>A	p.Pro506Pro	synonymous	Exon 2 of 3	ENSP00000414670.3
LMOD3	ENST00000475434.1	TSL:5	c.1518C>A	p.Pro506Pro	synonymous	Exon 3 of 4	ENSP00000418645.1
LMOD3	ENST00000489031.5	TSL:2	c.1518C>A	p.Pro506Pro	synonymous	Exon 3 of 4	ENSP00000417210.1

Frequencies

GnomAD3 genomes

AF:

0.000122

AC:

AN:

147412

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000755

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000274

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000135

Gnomad OTH

AF:

0.00100

GnomAD2 exomes

AF:

0.000129

AC:

AN:

248546

AF XY:

0.000111

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000247

AC:

361

AN:

1461568

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

157

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.000134

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000313

AC:

348

AN:

1111830

Other (OTH)

AF:

0.0000828

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000122

AC:

AN:

147412

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

71534

show subpopulations

African (AFR)

AF:

0.0000755

AC:

AN:

39744

American (AMR)

AF:

0.000274

AC:

AN:

14600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3398

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000135

AC:

AN:

66808

Other (OTH)

AF:

0.00100

AC:

AN:

1996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000893

Hom.:

Bravo

AF:

0.000196

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nemaline myopathy 10 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.042

(source)

DANN

Benign

0.51

PhyloP100

-5.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over