dbSNP rs2820312: LMOD1:p.Thr295Met (chr1-201900129-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_012134.3(LMOD1):c.884C>T(p.Thr295Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,506 control chromosomes in the GnomAD database, including 80,997 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T295S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.28 ( 6065 hom., cov: 31)

Exomes 𝑓: 0.31 ( 74932 hom. )

Consequence

LMOD1
NM_012134.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.115

Variant links:

Genes affected

LMOD1 (HGNC:6647): (leiomodin 1) The leiomodin 1 protein has a putative membrane-spanning region and 2 types of tandemly repeated blocks. The transcript is expressed in all tissues tested, with the highest levels in thyroid, eye muscle, skeletal muscle, and ovary. Increased expression of leiomodin 1 may be linked to Graves' disease and thyroid-associated ophthalmopathy. [provided by RefSeq, Jul 2008]

LMOD1 links:

ENSG00000223774 (HGNC:):

ENSG00000223774 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045855343).

BP6

Variant 1-201900129-G-A is Benign according to our data. Variant chr1-201900129-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMOD1	NM_012134.3 link	c.884C>T	p.Thr295Met	missense_variant	Exon 2 of 3	ENST00000367288.5	NP_036266.2	P29536-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMOD1	ENST00000367288.5 link	c.884C>T	p.Thr295Met	missense_variant	Exon 2 of 3	1	NM_012134.3	ENSP00000356257.4	P29536-1
ENSG00000223774	ENST00000414927.5 link	n.*151G>A		downstream_gene_variant		3
ENSG00000223774	ENST00000458139.1 link	n.*151G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42009

AN:

151862

Hom.:

6062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.278

AC:

69145

AN:

248924

Hom.:

10223

AF XY:

0.280

AC XY:

37807

AN XY:

135060

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.314

AC:

459377

AN:

1461524

Hom.:

74932

Cov.:

AF XY:

0.313

AC XY:

227470

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.216

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.192

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.277

AC:

42025

AN:

151982

Hom.:

6065

Cov.:

AF XY:

0.274

AC XY:

20382

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.313

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.300

Hom.:

17392

Bravo

AF:

0.270

TwinsUK

AF:

0.323

AC:

1199

ALSPAC

AF:

0.330

AC:

1273

ESP6500AA

AF:

0.206

AC:

830

ESP6500EA

AF:

0.314

AC:

2618

ExAC

AF:

0.278

AC:

33662

Asia WGS

AF:

0.160

AC:

555

AN:

3478

EpiCase

AF:

0.315

EpiControl

AF:

0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

3.8

DANN

Benign

0.86

DEOGEN2

Benign

0.12

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.46

REVEL

Benign

0.24

Sift

Benign

0.29

Sift4G

Benign

0.093

Polyphen

0.95

Vest4

0.028

MPC

0.40

ClinPred

0.0023

GERP RS

0.58

Varity_R

0.016

gMVP

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over