1-201900129-G-T

Variant names:

• chr1-201900129-G-T
• rs2820312
• NM_012134.3:c.884C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012134.3(LMOD1):​c.884C>A​(p.Thr295Lys) 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. 15/22 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. T295S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LMOD1 NM_012134.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 46 publications found

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 Gene-Disease associations (from GenCC):

• megacystis-microcolon-intestinal hypoperistalsis syndrome 3

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• megacystis-microcolon-intestinal hypoperistalsis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000223774 (HGNC:58701):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068656).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012134.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMOD1	NM_012134.3	MANE Select	c.884C>A	p.Thr295Lys	missense	Exon 2 of 3	NP_036266.2	P29536-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMOD1	ENST00000367288.5	TSL:1 MANE Select	c.884C>A	p.Thr295Lys	missense	Exon 2 of 3	ENSP00000356257.4	P29536-1
	LMOD1	ENST00000869075.1		c.262-1731C>A		intron	N/A	ENSP00000539134.1
	ENSG00000223774	ENST00000414927.5	TSL:3	n.*151G>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 23772

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.35
DANN	Benign	0.53
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.12
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.25	N
REVEL	Uncertain	0.31
Sift	Benign	0.15	T
Sift4G	Benign	0.82	T
Polyphen		0.0060	B
Vest4		0.17
MutPred		0.52		Loss of phosphorylation at T295 (P = 9e-04)
MVP		0.45
MPC		0.34
ClinPred		0.086	T
GERP RS		0.58
Varity_R		0.043
gMVP		0.12
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs2820312; hg19: chr1-201869257;