rs2820312

Variant summary

Our verdict is Benign. The variant received -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. 16/22 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

18

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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
LMOD1NM_012134.3 linkc.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 Appris UniProt
LMOD1ENST00000367288.5 linkc.884C>T p.Thr295Met missense_variant Exon 2 of 3 1 NM_012134.3 ENSP00000356257.4 P29536-1
ENSG00000223774ENST00000414927.5 linkn.*151G>A downstream_gene_variant 3
ENSG00000223774ENST00000458139.1 linkn.*151G>A downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.277
AC:
42009
AN:
151862
Hom.:
6062
Cov.:
31
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
GnomAD2 exomes
AF:
0.278
AC:
69145
AN:
248924
AF XY:
0.280
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 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.:
57
AF XY:
0.313
AC XY:
227470
AN XY:
727054
show subpopulations
Gnomad4 AFR exome
AF:
0.216
AC:
7236
AN:
33480
Gnomad4 AMR exome
AF:
0.256
AC:
11455
AN:
44690
Gnomad4 ASJ exome
AF:
0.192
AC:
5007
AN:
26136
Gnomad4 EAS exome
AF:
0.102
AC:
4060
AN:
39698
Gnomad4 SAS exome
AF:
0.281
AC:
24270
AN:
86256
Gnomad4 FIN exome
AF:
0.302
AC:
16129
AN:
53388
Gnomad4 NFE exome
AF:
0.335
AC:
372332
AN:
1111736
Gnomad4 Remaining exome
AF:
0.293
AC:
17717
AN:
60372
Heterozygous variant carriers
0
19278
38557
57835
77114
96392
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
11846
23692
35538
47384
59230
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.277
AC:
42025
AN:
151982
Hom.:
6065
Cov.:
31
AF XY:
0.274
AC XY:
20382
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.219
AC:
0.218797
AN:
0.218797
Gnomad4 AMR
AF:
0.265
AC:
0.265214
AN:
0.265214
Gnomad4 ASJ
AF:
0.189
AC:
0.189446
AN:
0.189446
Gnomad4 EAS
AF:
0.103
AC:
0.102907
AN:
0.102907
Gnomad4 SAS
AF:
0.261
AC:
0.260933
AN:
0.260933
Gnomad4 FIN
AF:
0.313
AC:
0.312666
AN:
0.312666
Gnomad4 NFE
AF:
0.328
AC:
0.327691
AN:
0.327691
Gnomad4 OTH
AF:
0.245
AC:
0.24455
AN:
0.24455
Heterozygous variant carriers
0
1543
3086
4630
6173
7716
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
434
868
1302
1736
2170
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.296
Hom.:
23772
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
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
3.8
DANN
Benign
0.86
DEOGEN2
Benign
0.12
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.20
T
MetaRNN
Benign
0.0046
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.24
Sift
Benign
0.29
T
Sift4G
Benign
0.093
T
Polyphen
0.95
P
Vest4
0.028
MPC
0.40
ClinPred
0.0023
T
GERP RS
0.58
Varity_R
0.016
gMVP
0.12
Mutation Taster
=100/0
polymorphism (auto)

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.

Other links and lift over

dbSNP: rs2820312; hg19: chr1-201869257; COSMIC: COSV66172120; COSMIC: COSV66172120; API