14-55142700-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002306.4(LGALS3):c.548G>A(p.Arg183Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,613,880 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.026 (164 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (162 hom.)
• Consequence: LGALS3 NM_002306.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036584735).
• BP6: Variant 14-55142700-G-A is Benign according to our data. Variant chr14-55142700-G-A is described in ClinVar as [Benign]. Clinvar id is 768654.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS3	NM_002306.4	c.548G>A	p.Arg183Lys	missense_variant	5/6	ENST00000254301.14
LGALS3	NM_001357678.2	c.590G>A	p.Arg197Lys	missense_variant	6/7
LGALS3	NR_003225.2	n.1592G>A		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS3	ENST00000254301.14	c.548G>A	p.Arg183Lys	missense_variant	5/6	1	NM_002306.4	P1

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3920 AN: 152166 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00824

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00689 AC: 1719 AN: 249528 Hom.: 77 AF XY: 0.00553 AC XY: 748 AN XY: 135384

Gnomad AFR exome AF: 0.0949

Gnomad AMR exome AF: 0.00507

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00272 AC: 3973 AN: 1461596 Hom.: 162 Cov.: 30 AF XY: 0.00239 AC XY: 1738 AN XY: 727128

Gnomad4 AFR exome AF: 0.0933

Gnomad4 AMR exome AF: 0.00552

Gnomad4 ASJ exome AF: 0.00367

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.00518

GnomAD4 genome AF: 0.0258 AC: 3926 AN: 152284 Hom.: 164 Cov.: 32 AF XY: 0.0247 AC XY: 1840 AN XY: 74478

Gnomad4 AFR AF: 0.0901

Gnomad4 AMR AF: 0.00823

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00531 Hom.: 48

Bravo AF: 0.0294

ESP6500AA AF: 0.0957 AC: 353

ESP6500EA AF: 0.000244 AC: 2

ExAC AF: 0.00874 AC: 1056

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000437

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.024
Dann	Benign	0.64
DEOGEN2	Benign	0.036	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.51	T;T
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.050	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.73	N;N
REVEL	Benign	0.021
Sift	Benign	1.0	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.0	B;.
Vest4		0.11
MVP		0.19
MPC		0.064
ClinPred		0.99	D
GERP RS		-9.0
Varity_R		0.19
gMVP		0.35

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: rs10148371; hg19: chr14-55609418;