NM_052972.3:c.397C>A

Variant names:

• chr19-4538587-G-T
• rs966384
• NM_052972.3:c.397C>A

Variant summary

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

The NM_052972.3(LRG1):​c.397C>A​(p.Pro133Thr) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRG1 NM_052972.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 0 publications found

Genes affected

LRG1 (HGNC:29480): (leucine rich alpha-2-glycoprotein 1) The leucine-rich repeat (LRR) family of proteins, including LRG1, have been shown to be involved in protein-protein interaction, signal transduction, and cell adhesion and development. LRG1 is expressed during granulocyte differentiation (O'Donnell et al., 2002 [PubMed 12223515]).[supplied by OMIM, Mar 2008]

ENSG00000267385 (HGNC:):

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=0.15184364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052972.3. 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
	LRG1	NM_052972.3	MANE Select	c.397C>A	p.Pro133Thr	missense	Exon 2 of 2	NP_443204.1	P02750

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRG1	ENST00000306390.7	TSL:1 MANE Select	c.397C>A	p.Pro133Thr	missense	Exon 2 of 2	ENSP00000302621.4	P02750
	ENSG00000267385	ENST00000586020.1	TSL:2	n.32+1395C>A		intron	N/A	ENSP00000464793.1	K7EIL1
	LRG1	ENST00000885090.1		c.367C>A	p.Pro123Thr	missense	Exon 2 of 2	ENSP00000555149.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.089
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.050
Sift	Benign	0.033	D
Sift4G	Benign	0.24	T
Polyphen		0.80	P
Vest4		0.067
MutPred		0.33		Gain of catalytic residue at P133 (P = 0.0112)
MVP		0.48
MPC		0.22
ClinPred		0.66	D
GERP RS		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.47
Mutation Taster		=89/11	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: rs966384; hg19: chr19-4538599;