14-55145121-A-T

Variant names:

• chr14-55145121-A-T
• rs11125
• NM_002306.4:c.603A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002306.4(LGALS3):​c.603A>T​(p.Gln201His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 1,612,430 control chromosomes in the GnomAD database, including 4,848 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.057 (310 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4538 hom.)
• Consequence: LGALS3 NM_002306.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 30 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023002028).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS3	NM_002306.4	c.603A>T	p.Gln201His	missense_variant	Exon 6 of 6	ENST00000254301.14	NP_002297.2
LGALS3	NM_001357678.2	c.645A>T	p.Gln215His	missense_variant	Exon 7 of 7		NP_001344607.1
LGALS3	NR_003225.2	n.1647A>T		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS3	ENST00000254301.14	c.603A>T	p.Gln201His	missense_variant	Exon 6 of 6	1	NM_002306.4	ENSP00000254301.9
LGALS3	ENST00000556438.6	n.1442A>T		non_coding_transcript_exon_variant	Exon 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8699 AN: 152152 Hom.: 310 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0641

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0626

GnomAD2 exomes AF: 0.0651 AC: 16210 AN: 248824 AF XY: 0.0685

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0415

Gnomad ASJ exome AF: 0.0629

Gnomad EAS exome AF: 0.00167

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.0803

Gnomad OTH exome AF: 0.0692

GnomAD4 exome AF: 0.0758 AC: 110683 AN: 1460160 Hom.: 4538 Cov.: 31 AF XY: 0.0764 AC XY: 55505 AN XY: 726504

African (AFR) AF: 0.0119 AC: 397 AN: 33442

American (AMR) AF: 0.0436 AC: 1942 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 1604 AN: 26098

East Asian (EAS) AF: 0.00116 AC: 46 AN: 39688

South Asian (SAS) AF: 0.0953 AC: 8212 AN: 86198

European-Finnish (FIN) AF: 0.0752 AC: 4017 AN: 53404

Middle Eastern (MID) AF: 0.0579 AC: 334 AN: 5766

European-Non Finnish (NFE) AF: 0.0810 AC: 90007 AN: 1110644

Other (OTH) AF: 0.0683 AC: 4124 AN: 60338

GnomAD4 genome AF: 0.0571 AC: 8701 AN: 152270 Hom.: 310 Cov.: 32 AF XY: 0.0570 AC XY: 4244 AN XY: 74448

African (AFR) AF: 0.0137 AC: 568 AN: 41570

American (AMR) AF: 0.0640 AC: 979 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5182

South Asian (SAS) AF: 0.0906 AC: 437 AN: 4822

European-Finnish (FIN) AF: 0.0741 AC: 785 AN: 10588

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5419 AN: 68020

Other (OTH) AF: 0.0620 AC: 131 AN: 2114

Alfa AF: 0.0687 Hom.: 293

Bravo AF: 0.0533

TwinsUK AF: 0.0812 AC: 301

ALSPAC AF: 0.0747 AC: 288

ESP6500AA AF: 0.0137 AC: 53

ESP6500EA AF: 0.0769 AC: 636

ExAC AF: 0.0663 AC: 8013

Asia WGS AF: 0.0350 AC: 120 AN: 3478

EpiCase AF: 0.0780

EpiControl AF: 0.0799

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.041
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.21
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.13
Sift	Benign	0.032	D
Sift4G	Benign	0.51	T
Polyphen		1.0	D
Vest4		0.099
MutPred		0.51		Gain of ubiquitination at K196 (P = 0.0797);
MPC		0.22
ClinPred		0.046	T
GERP RS		2.4
Varity_R		0.65
gMVP		0.76
Mutation Taster		=55/45	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11125; hg19: chr14-55611839; COSMIC: COSV54306030; COSMIC: COSV54306030;