14-55138157-C-A

Variant names:

• chr14-55138157-C-A
• rs1021922683
• NM_002306.4:c.131C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002306.4(LGALS3):​c.131C>A​(p.Ala44Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A44V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LGALS3 NM_002306.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36189732).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS3	NM_002306.4	MANE Select	c.131C>A	p.Ala44Asp	missense	Exon 3 of 6	NP_002297.2	P17931
	LGALS3	NM_001357678.2		c.173C>A	p.Ala58Asp	missense	Exon 4 of 7	NP_001344607.1
	LGALS3	NR_003225.2		n.1175C>A		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS3	ENST00000254301.14	TSL:1 MANE Select	c.131C>A	p.Ala44Asp	missense	Exon 3 of 6	ENSP00000254301.9	P17931
	LGALS3	ENST00000556438.6	TSL:1	n.970C>A		non_coding_transcript_exon	Exon 1 of 4
	LGALS3	ENST00000947958.1		c.272C>A	p.Ala91Asp	missense	Exon 4 of 7	ENSP00000618017.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1450070 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721054

African (AFR) AF: 0.00 AC: 0 AN: 32810

American (AMR) AF: 0.00 AC: 0 AN: 41744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25252

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 84368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107836

Other (OTH) AF: 0.0000167 AC: 1 AN: 59772

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.025	D
Polyphen		0.74	P
Vest4		0.47
MutPred		0.16		Loss of glycosylation at P46 (P = 0.0882)
MVP		0.90
MPC		0.089
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.36
Mutation Taster		=64/36	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: rs1021922683; hg19: chr14-55604875;