3-69108999-G-A

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.*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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.988

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=-0.53).
• 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	UniProt
LMOD3	NM_198271.5	c.*96C>T		3_prime_UTR_variant	3/3	ENST00000420581.7
LMOD3	NM_001304418.3	c.*96C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMOD3	ENST00000420581.7	c.*96C>T		3_prime_UTR_variant	3/3	1	NM_198271.5	P1
LMOD3	ENST00000475434.1	c.*96C>T		3_prime_UTR_variant	4/4	5		P1
LMOD3	ENST00000489031.5	c.*96C>T		3_prime_UTR_variant	4/4	2		P1

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4576 AN: 151916 Hom.: 200 Cov.: 31

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.: 12 AF XY: 0.00560 AC XY: 2673 AN XY: 477702

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.: 31 AF XY: 0.0296 AC XY: 2199 AN XY: 74308

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.: 17

Bravo AF: 0.0349

Asia WGS AF: 0.0270 AC: 95 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

Jul 27, 2018

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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

Other links and lift over

dbSNP: rs72924865; hg19: chr3-69158150; COSMIC: COSV56235042; COSMIC: COSV56235042;