Variant chr3-69108999-G-A 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.*96C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00935 in 1,087,860 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 201 hom., cov: 31)

Exomes 𝑓: 0.0060 ( 211 hom. )

Consequence

LMOD3
NM_198271.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.988

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=-0.53).

BP6

Variant 3-69108999-G-A is Benign according to our data. Variant chr3-69108999-G-A is described in ClinVar as [Benign]. Clinvar id is 1278003.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0938 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.*96C>T		3_prime_UTR_variant	3/3	ENST00000420581.7	NP_938012.2
LMOD3	NM_001304418.3 linkuse as main transcript	c.*96C>T		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.*96C>T	3_prime_UTR_variant	3/3	1	NM_198271.5	ENSP00000414670	P1	Q0VAK6-1
LMOD3	ENST00000475434.1 linkuse as main transcript	c.*96C>T	3_prime_UTR_variant	4/4	5		ENSP00000418645	P1	Q0VAK6-1
LMOD3	ENST00000489031.5 linkuse as main transcript	c.*96C>T	3_prime_UTR_variant	4/4	2		ENSP00000417210	P1	Q0VAK6-1

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

4576

AN:

151916

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0961

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0542

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.0205

GnomAD4 exome

AF:

0.00596

AC:

5575

AN:

935828

Hom.:

211

Cov.:

AF XY:

0.00560

AC XY:

2673

AN XY:

477702

show subpopulations

Gnomad4 AFR exome

AF:

0.0947

Gnomad4 AMR exome

AF:

0.00744

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0651

Gnomad4 SAS exome

AF:

0.00621

Gnomad4 FIN exome

AF:

0.000322

Gnomad4 NFE exome

AF:

0.000318

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0302

AC:

4597

AN:

152032

Hom.:

201

Cov.:

AF XY:

0.0296

AC XY:

2199

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0963

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0545

Gnomad4 SAS

AF:

0.00954

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0135

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

-0.53

CADD

Benign

8.2

DANN

Benign

0.94

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