Genetic Variant NM_012134.3:c.1430A>G (chr1-201899583-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_012134.3(LMOD1):c.1430A>G(p.Lys477Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K477T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

LMOD1
NM_012134.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.852

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:

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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=0.21291643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMOD1	NM_012134.3 link	c.1430A>G	p.Lys477Arg	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.1430A>G	p.Lys477Arg	missense_variant	Exon 2 of 3	1	NM_012134.3	ENSP00000356257.4	P29536-1
ENSG00000223774	ENST00000414927.5 link	n.246-147T>C		intron_variant	Intron 2 of 2	3
ENSG00000223774	ENST00000458139.1 link	n.352-147T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.049

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.037

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.0

REVEL

Benign

0.27

Sift

Benign

0.25

Sift4G

Benign

0.22

Polyphen

0.93

Vest4

0.12

MutPred

0.42

Loss of methylation at K477 (P = 0.0146);

MVP

0.55

MPC

0.25

ClinPred

0.68

GERP RS

3.4

Varity_R

0.28

gMVP

0.39

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over