3-69109080-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198271.5(LMOD3):c.*15A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,593,222 control chromosomes in the GnomAD database, including 2,886 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: 32)
  • Exomes 𝑓: 0.026 (2581 hom.)
• Consequence: LMOD3 NM_198271.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0830

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-69109080-T-C is Benign according to our data. Variant chr3-69109080-T-C is described in ClinVar as [Benign]. Clinvar id is 1180899.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
LMOD3	NM_198271.5	c.*15A>G		3_prime_UTR_variant	3/3	ENST00000420581.7
LMOD3	NM_001304418.3	c.*15A>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMOD3	ENST00000420581.7	c.*15A>G		3_prime_UTR_variant	3/3	1	NM_198271.5	P1
LMOD3	ENST00000475434.1	c.*15A>G		3_prime_UTR_variant	4/4	5		P1
LMOD3	ENST00000489031.5	c.*15A>G		3_prime_UTR_variant	4/4	2		P1

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5440 AN: 152196 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0311

GnomAD3 exomes AF: 0.0498 AC: 10792 AN: 216830 Hom.: 965 AF XY: 0.0516 AC XY: 6028 AN XY: 116870

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.0243

Gnomad ASJ exome AF: 0.0149

Gnomad EAS exome AF: 0.282

Gnomad SAS exome AF: 0.133

Gnomad FIN exome AF: 0.00382

Gnomad NFE exome AF: 0.00912

Gnomad OTH exome AF: 0.0337

GnomAD4 exome AF: 0.0265 AC: 38140 AN: 1440908 Hom.: 2581 Cov.: 29 AF XY: 0.0292 AC XY: 20870 AN XY: 714956

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.0231

Gnomad4 ASJ exome AF: 0.0152

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.00487

Gnomad4 NFE exome AF: 0.00980

Gnomad4 OTH exome AF: 0.0338

GnomAD4 genome AF: 0.0358 AC: 5453 AN: 152314 Hom.: 305 Cov.: 32 AF XY: 0.0395 AC XY: 2944 AN XY: 74484

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0184 Hom.: 22

Bravo AF: 0.0373

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.81
Cadd	Benign	1.3
Dann	Benign	0.43

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

Other links and lift over

dbSNP: rs60474520; hg19: chr3-69158231; COSMIC: COSV56235588; COSMIC: COSV56235588;