NM_002306.4:c.191C>G

Variant names:

• chr14-55138217-C-G
• rs4644
• NM_002306.4:c.191C>G

Variant summary

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

The NM_002306.4(LGALS3):​c.191C>G​(p.Pro64Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGALS3 NM_002306.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61
• Publications: 107 publications found

Genes affected

LGALS3 (HGNC:6563): (galectin 3) This gene encodes a member of the galectin family of carbohydrate binding proteins. Members of this protein family have an affinity for beta-galactosides. The encoded protein is characterized by an N-terminal proline-rich tandem repeat domain and a single C-terminal carbohydrate recognition domain. This protein can self-associate through the N-terminal domain allowing it to bind to multivalent saccharide ligands. This protein localizes to the extracellular matrix, the cytoplasm and the nucleus. This protein plays a role in numerous cellular functions including apoptosis, innate immunity, cell adhesion and T-cell regulation. The protein exhibits antimicrobial activity against bacteria and fungi. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2014]

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_002306.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS3	NM_002306.4	MANE Select	c.191C>G	p.Pro64Arg	missense	Exon 3 of 6	NP_002297.2
	LGALS3	NM_001357678.2		c.233C>G	p.Pro78Arg	missense	Exon 4 of 7	NP_001344607.1
	LGALS3	NR_003225.2		n.1235C>G		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS3	ENST00000254301.14	TSL:1 MANE Select	c.191C>G	p.Pro64Arg	missense	Exon 3 of 6	ENSP00000254301.9
	LGALS3	ENST00000556438.6	TSL:1	n.1030C>G		non_coding_transcript_exon	Exon 1 of 4
	LGALS3	ENST00000554715.1	TSL:3	c.191C>G	p.Pro64Arg	missense	Exon 3 of 6	ENSP00000451381.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 32730

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.23		Gain of methylation at P64 (P = 0.0037)
MVP		0.95
MPC		0.064
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.37
gMVP		0.83
Mutation Taster		=77/23	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: rs4644; hg19: chr14-55604935;