14-55138217-C-G

Position:

• chr14-55138217-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P64H) has been classified as Likely benign.

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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS3	NM_002306.4	c.191C>G	p.Pro64Arg	missense_variant	3/6	ENST00000254301.14
LGALS3	NM_001357678.2	c.233C>G	p.Pro78Arg	missense_variant	4/7
LGALS3	NR_003225.2	n.1235C>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS3	ENST00000254301.14	c.191C>G	p.Pro64Arg	missense_variant	3/6	1	NM_002306.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T;D;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	0.42	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-8.0	D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.67, 0.62
MutPred		0.23		Gain of methylation at P64 (P = 0.0037);Gain of methylation at P64 (P = 0.0037);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4644; hg19: chr14-55604935;