chr1-201899788-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_012134.3(LMOD1):​c.1225C>T​(p.Arg409Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

LMOD1
NM_012134.3 missense

Scores

10
8
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.51
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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LMOD1NM_012134.3 linkuse as main transcriptc.1225C>T p.Arg409Trp missense_variant 2/3 ENST00000367288.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LMOD1ENST00000367288.5 linkuse as main transcriptc.1225C>T p.Arg409Trp missense_variant 2/31 NM_012134.3 P1P29536-1
ENST00000414927.5 linkuse as main transcriptn.304G>A non_coding_transcript_exon_variant 3/33
ENST00000458139.1 linkuse as main transcriptn.410G>A non_coding_transcript_exon_variant 3/33

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000321
AC:
8
AN:
249010
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135068
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000709
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461692
Hom.:
0
Cov.:
39
AF XY:
0.00000550
AC XY:
4
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000660
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 20, 2023The c.1225C>T (p.R409W) alteration is located in exon 2 (coding exon 2) of the LMOD1 gene. This alteration results from a C to T substitution at nucleotide position 1225, causing the arginine (R) at amino acid position 409 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.65
D
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Pathogenic
0.47
D
MetaRNN
Pathogenic
0.90
D
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-6.5
D
REVEL
Pathogenic
0.75
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.79
MutPred
0.61
Loss of solvent accessibility (P = 0.1202);
MVP
0.82
MPC
0.95
ClinPred
0.97
D
GERP RS
4.5
Varity_R
0.70
gMVP
0.81

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: rs759999105; hg19: chr1-201868916; API