Variant 3-69109147-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198271.5(LMOD3):c.1657-26C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00755 in 1,593,666 control chromosomes in the GnomAD database, including 485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 202 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 283 hom. )

Consequence

LMOD3
NM_198271.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.171

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-69109147-G-C is Benign according to our data. Variant chr3-69109147-G-C is described in ClinVar as [Benign]. Clinvar id is 1242359.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0939 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.1657-26C>G		intron_variant		ENST00000420581.7	NP_938012.2
LMOD3	NM_001304418.3 linkuse as main transcript	c.1657-26C>G		intron_variant			NP_001291347.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
LMOD3	ENST00000420581.7 linkuse as main transcript	c.1657-26C>G	intron_variant	1	NM_198271.5	ENSP00000414670	P1	Q0VAK6-1
LMOD3	ENST00000475434.1 linkuse as main transcript	c.1657-26C>G	intron_variant	5		ENSP00000418645	P1	Q0VAK6-1
LMOD3	ENST00000489031.5 linkuse as main transcript	c.1657-26C>G	intron_variant	2		ENSP00000417210	P1	Q0VAK6-1

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

4583

AN:

152092

Hom.:

201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0962

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0543

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0110

AC:

2333

AN:

212876

Hom.:

AF XY:

0.00954

AC XY:

1094

AN XY:

114728

show subpopulations

Gnomad AFR exome

AF:

0.0970

Gnomad AMR exome

AF:

0.00590

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0406

Gnomad SAS exome

AF:

0.00598

Gnomad FIN exome

AF:

0.0000536

Gnomad NFE exome

AF:

0.000516

Gnomad OTH exome

AF:

0.00608

GnomAD4 exome

AF:

0.00515

AC:

7426

AN:

1441456

Hom.:

283

Cov.:

AF XY:

0.00484

AC XY:

3464

AN XY:

715164

show subpopulations

Gnomad4 AFR exome

AF:

0.0977

Gnomad4 AMR exome

AF:

0.00682

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0621

Gnomad4 SAS exome

AF:

0.00617

Gnomad4 FIN exome

AF:

0.000291

Gnomad4 NFE exome

AF:

0.000261

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.0302

AC:

4604

AN:

152210

Hom.:

202

Cov.:

AF XY:

0.0297

AC XY:

2210

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0964

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0546

Gnomad4 SAS

AF:

0.00891

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.0349

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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