dbSNP rs1233176003: LMOD1:p.Gln559Arg (chr1-201899337-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012134.3(LMOD1):c.1676A>G(p.Gln559Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000828 in 1,570,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

LMOD1
NM_012134.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30358988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMOD1	NM_012134.3 link	c.1676A>G	p.Gln559Arg	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.1676A>G	p.Gln559Arg	missense_variant	Exon 2 of 3	1	NM_012134.3	ENSP00000356257.4	P29536-1
ENSG00000223774	ENST00000414927.5 link	n.236T>C		non_coding_transcript_exon_variant	Exon 2 of 3	3
ENSG00000223774	ENST00000458139.1 link	n.342T>C		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0000141

AC:

AN:

142120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000306

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000770

AC:

AN:

1428688

Hom.:

Cov.:

AF XY:

0.00000704

AC XY:

AN XY:

710610

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:

0.0000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000141

AC:

AN:

142120

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

68804

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000306

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1676A>G (p.Q559R) alteration is located in exon 2 (coding exon 2) of the LMOD1 gene. This alteration results from a A to G substitution at nucleotide position 1676, causing the glutamine (Q) at amino acid position 559 to be replaced by an arginine (R). 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

Benign

0.23

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.30

T;T

MetaSVM

Uncertain

0.47

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.5

N;.

REVEL

Uncertain

0.37

Sift

Benign

0.041

D;.

Sift4G

Uncertain

0.019

D;D

Polyphen

0.99

D;.

Vest4

0.36

MutPred

0.13

Loss of ubiquitination at K561 (P = 0.0183);.;

MVP

0.50

MPC

0.96

ClinPred

0.89

GERP RS

5.0

Varity_R

0.24

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over