Variant rs72924884 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000420581.7(LMOD3):c.1270T>C(p.Leu424=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,613,488 control chromosomes in the GnomAD database, including 827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 153 hom., cov: 31)

Exomes 𝑓: 0.026 ( 674 hom. )

Consequence

LMOD3
ENST00000420581.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.551

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-69119085-A-G is Benign according to our data. Variant chr3-69119085-A-G is described in ClinVar as [Benign]. Clinvar id is 475300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.551 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMOD3	NM_198271.5 linkuse as main transcript	c.1270T>C	p.Leu424=	synonymous_variant	2/3	ENST00000420581.7	NP_938012.2
LMOD3	NM_001304418.3 linkuse as main transcript	c.1270T>C	p.Leu424=	synonymous_variant	3/4		NP_001291347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMOD3	ENST00000420581.7 linkuse as main transcript	c.1270T>C	p.Leu424=	synonymous_variant	2/3	1	NM_198271.5	ENSP00000414670	P1	Q0VAK6-1
LMOD3	ENST00000475434.1 linkuse as main transcript	c.1270T>C	p.Leu424=	synonymous_variant	3/4	5		ENSP00000418645	P1	Q0VAK6-1
LMOD3	ENST00000489031.5 linkuse as main transcript	c.1270T>C	p.Leu424=	synonymous_variant	3/4	2		ENSP00000417210	P1	Q0VAK6-1

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

5805

AN:

151674

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0581

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0634

Gnomad ASJ

AF:

0.00636

Gnomad EAS

AF:

0.0503

Gnomad SAS

AF:

0.0249

Gnomad FIN

AF:

0.0640

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0365

AC:

9088

AN:

249132

Hom.:

260

AF XY:

0.0334

AC XY:

4515

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.0630

Gnomad AMR exome

AF:

0.0826

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.0510

Gnomad SAS exome

AF:

0.0210

Gnomad FIN exome

AF:

0.0627

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0333

GnomAD4 exome

AF:

0.0256

AC:

37426

AN:

1461696

Hom.:

674

Cov.:

AF XY:

0.0250

AC XY:

18202

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.0596

Gnomad4 AMR exome

AF:

0.0830

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0549

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.0567

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0312

GnomAD4 genome

AF:

0.0383

AC:

5812

AN:

151792

Hom.:

153

Cov.:

AF XY:

0.0400

AC XY:

2965

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.0579

Gnomad4 AMR

AF:

0.0640

Gnomad4 ASJ

AF:

0.00636

Gnomad4 EAS

AF:

0.0500

Gnomad4 SAS

AF:

0.0240

Gnomad4 FIN

AF:

0.0640

Gnomad4 NFE

AF:

0.0189

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0411

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

EpiCase

AF:

0.0186

EpiControl

AF:

0.0181

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nemaline myopathy 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.37

DANN

Benign

0.60

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over