chr1-201899580-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_012134.3(LMOD1):​c.1433G>A​(p.Arg478Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,708 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: 0.0000021 ( 0 hom. )

Consequence

LMOD1
NM_012134.3 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LMOD1NM_012134.3 linkuse as main transcriptc.1433G>A p.Arg478Gln missense_variant 2/3 ENST00000367288.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LMOD1ENST00000367288.5 linkuse as main transcriptc.1433G>A p.Arg478Gln missense_variant 2/31 NM_012134.3 P1P29536-1
ENST00000414927.5 linkuse as main transcriptn.246-150C>T intron_variant, non_coding_transcript_variant 3
ENST00000458139.1 linkuse as main transcriptn.352-150C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000406
AC:
1
AN:
246038
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133538
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:
0.00000899
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460708
Hom.:
0
Cov.:
40
AF XY:
0.00000138
AC XY:
1
AN XY:
726568
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

Megacystis-microcolon-intestinal hypoperistalsis syndrome 3 Uncertain:1
Uncertain significance, criteria provided, single submitterresearchCenter for Genomic Medicine, King Faisal Specialist Hospital and Research CenterMar 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Benign
0.0022
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.60
D
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Uncertain
0.093
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.9
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-3.7
D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.69
MutPred
0.67
Gain of ubiquitination at K477 (P = 0.0231);
MVP
0.49
MPC
1.0
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.86
gMVP
0.72

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: rs1363706242; hg19: chr1-201868708; API