Variant chr3-69108943-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198271.5(LMOD3):c.*152A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 637,716 control chromosomes in the GnomAD database, including 1,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 305 hom., cov: 31)

Exomes 𝑓: 0.038 ( 1604 hom. )

Consequence

LMOD3
NM_198271.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.235

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 3-69108943-T-G is Benign according to our data. Variant chr3-69108943-T-G is described in ClinVar as [Benign]. Clinvar id is 1222613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 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.*152A>C		3_prime_UTR_variant	3/3	ENST00000420581.7	NP_938012.2
LMOD3	NM_001304418.3 linkuse as main transcript	c.*152A>C		3_prime_UTR_variant	4/4		NP_001291347.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMOD3	ENST00000420581.7 linkuse as main transcript	c.*152A>C	3_prime_UTR_variant	3/3	1	NM_198271.5	ENSP00000414670	P1	Q0VAK6-1
LMOD3	ENST00000475434.1 linkuse as main transcript	c.*152A>C	3_prime_UTR_variant	4/4	5		ENSP00000418645	P1	Q0VAK6-1
LMOD3	ENST00000489031.5 linkuse as main transcript	c.*152A>C	3_prime_UTR_variant	4/4	2		ENSP00000417210	P1	Q0VAK6-1

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5435

AN:

152160

Hom.:

302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0550

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0311

GnomAD4 exome

AF:

0.0378

AC:

18341

AN:

485436

Hom.:

1604

Cov.:

AF XY:

0.0414

AC XY:

10563

AN XY:

254956

show subpopulations

Gnomad4 AFR exome

AF:

0.0565

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.275

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.00473

Gnomad4 NFE exome

AF:

0.00930

Gnomad4 OTH exome

AF:

0.0310

GnomAD4 genome

AF:

0.0358

AC:

5448

AN:

152280

Hom.:

305

Cov.:

AF XY:

0.0395

AC XY:

2944

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0552

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.265

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0183

Hom.:

Bravo

AF:

0.0372

Asia WGS

AF:

0.159

AC:

555

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.3

DANN

Benign

0.87

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