1-201899382-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012134.3(LMOD1):​c.1631C>A​(p.Pro544His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,613,012 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00030 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

LMOD1
NM_012134.3 missense

Scores

6
5
8

Clinical Significance

Uncertain significance no assertion criteria provided U:2

Conservation

PhyloP100: 7.63
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19708315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LMOD1NM_012134.3 linkuse as main transcriptc.1631C>A p.Pro544His missense_variant 2/3 ENST00000367288.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LMOD1ENST00000367288.5 linkuse as main transcriptc.1631C>A p.Pro544His missense_variant 2/31 NM_012134.3 P1P29536-1
ENST00000414927.5 linkuse as main transcriptn.245+36G>T intron_variant, non_coding_transcript_variant 3
ENST00000458139.1 linkuse as main transcriptn.351+36G>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000296
AC:
45
AN:
152076
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000412
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.000316
AC:
78
AN:
247068
Hom.:
0
AF XY:
0.000373
AC XY:
50
AN XY:
134030
show subpopulations
Gnomad AFR exome
AF:
0.0000658
Gnomad AMR exome
AF:
0.000233
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000467
Gnomad NFE exome
AF:
0.000599
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.000464
AC:
678
AN:
1460818
Hom.:
0
Cov.:
45
AF XY:
0.000449
AC XY:
326
AN XY:
726554
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000314
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000578
Gnomad4 OTH exome
AF:
0.000315
GnomAD4 genome
AF:
0.000296
AC:
45
AN:
152194
Hom.:
1
Cov.:
31
AF XY:
0.000282
AC XY:
21
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000412
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000450
Hom.:
0
Bravo
AF:
0.000393
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000614
AC:
5
ExAC
AF:
0.000406
AC:
49

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:2
Uncertain significance, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Uncertain significance, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D;.
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.083
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.8
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.0
D;.
REVEL
Uncertain
0.34
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
D;.
Vest4
0.65
MVP
0.28
MPC
1.0
ClinPred
0.45
T
GERP RS
4.8
Varity_R
0.55
gMVP
0.44

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: rs202184893; hg19: chr1-201868510; API