rs4644

chr14-55138217-C-Achr14-55138217-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002306.4(LGALS3):c.191C>A(p.Pro64His) variant causes a missense change. The variant allele was found at a frequency of 0.389 in 1,613,016 control chromosomes in the GnomAD database, including 125,766 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.36 (10258 hom., cov: 32)
  • Exomes 𝑓: 0.39 (115508 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030170083).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS3	NM_002306.4	c.191C>A	p.Pro64His	missense_variant	3/6	ENST00000254301.14
LGALS3	NM_001357678.2	c.233C>A	p.Pro78His	missense_variant	4/7
LGALS3	NR_003225.2	n.1235C>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS3	ENST00000254301.14	c.191C>A	p.Pro64His	missense_variant	3/6	1	NM_002306.4	P1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54259 AN: 151874 Hom.: 10247 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.327

GnomAD3 exomes AF: 0.351 AC: 86468 AN: 246424 Hom.: 16543 AF XY: 0.358 AC XY: 48072 AN XY: 134418

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.192

Gnomad SAS exome AF: 0.369

Gnomad FIN exome AF: 0.514

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.393 AC: 573600 AN: 1461024 Hom.: 115508 Cov.: 52 AF XY: 0.392 AC XY: 284784 AN XY: 726828

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.357 AC: 54298 AN: 151992 Hom.: 10258 Cov.: 32 AF XY: 0.360 AC XY: 26770 AN XY: 74306

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.325

Alfa AF: 0.369 Hom.: 22698

Bravo AF: 0.332

TwinsUK AF: 0.407 AC: 1509

ALSPAC AF: 0.408 AC: 1573

ESP6500AA AF: 0.279 AC: 1015

ESP6500EA AF: 0.398 AC: 3240

ExAC AF: 0.351 AC: 42334

Asia WGS AF: 0.289 AC: 1005 AN: 3478

EpiCase AF: 0.378

EpiControl AF: 0.369

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
Cadd	Benign	22
Dann	Benign	0.96
DEOGEN2	Benign	0.21	T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.57	T;T;T
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-1.2	T
MutationTaster	Benign	0.000035	P;P
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-8.0	D;D;D
REVEL	Benign	0.18
Sift	Benign	0.052	T;D;D
Sift4G	Pathogenic	0.0	D;T;D
Polyphen		1.0	.;D;.
Vest4		0.37, 0.25
MPC		0.069
ClinPred		0.11	T
GERP RS		5.7
Varity_R		0.34
gMVP		0.77

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;