rs202184893

Variant names:

• chr1-201899382-G-C
• rs202184893
• NM_012134.3:c.1631C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-201899382-G-C
• chr1-201899382-G-T

Variant summary

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

The NM_012134.3(LMOD1):​c.1631C>G​(p.Pro544Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P544H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LMOD1 NM_012134.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63
• Publications: 2 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: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• megacystis-microcolon-intestinal hypoperistalsis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000223774 (HGNC:58701):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1631C>G	p.Pro544Arg	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.1631C>G	p.Pro544Arg	missense	Exon 2 of 3	ENSP00000356257.4	P29536-1
	LMOD1	ENST00000869075.1		c.262-984C>G		intron	N/A	ENSP00000539134.1
	ENSG00000223774	ENST00000414927.5	TSL:3	n.245+36G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 247068 AF XY: 0.00000746

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460820 Hom.: 0 Cov.: 45 AF XY: 0.00000138 AC XY: 1 AN XY: 726554

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111438

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.070	T
Polyphen		1.0	D
Vest4		0.69
MutPred		0.24		Gain of MoRF binding (P = 0.0199)
MVP		0.22
MPC		0.96
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.46
gMVP		0.55
Mutation Taster		=80/20	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: rs202184893; hg19: chr1-201868510;