chr14-55138320-C-T

Variant names:

• chr14-55138320-C-T
• rs78964872
• NM_002306.4:c.294C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002306.4(LGALS3):​c.294C>T​(p.Thr98Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,612,398 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (31 hom., cov: 33)
  • Exomes 𝑓: 0.00099 (26 hom.)
• Consequence: LGALS3 NM_002306.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.905
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 14-55138320-C-T is Benign according to our data. Variant chr14-55138320-C-T is described in ClinVar as Benign. ClinVar VariationId is 776843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.905 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00924 (1408/152302) while in subpopulation AFR AF = 0.0326 (1353/41558). AF 95% confidence interval is 0.0311. There are 31 homozygotes in GnomAd4. There are 645 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

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.294C>T	p.Thr98Thr	synonymous	Exon 3 of 6	NP_002297.2	P17931
	LGALS3	NM_001357678.2		c.336C>T	p.Thr112Thr	synonymous	Exon 4 of 7	NP_001344607.1
	LGALS3	NR_003225.2		n.1338C>T		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.294C>T	p.Thr98Thr	synonymous	Exon 3 of 6	ENSP00000254301.9	P17931
	LGALS3	ENST00000556438.6	TSL:1	n.1133C>T		non_coding_transcript_exon	Exon 1 of 4
	LGALS3	ENST00000947958.1		c.435C>T	p.Thr145Thr	synonymous	Exon 4 of 7	ENSP00000618017.1

Frequencies

GnomAD3 genomes AF: 0.00923 AC: 1405 AN: 152184 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00218 AC: 529 AN: 242294 AF XY: 0.00156

Gnomad AFR exome AF: 0.0332

Gnomad AMR exome AF: 0.00129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000644

Gnomad OTH exome AF: 0.000673

GnomAD4 exome AF: 0.000987 AC: 1441 AN: 1460096 Hom.: 26 Cov.: 33 AF XY: 0.000807 AC XY: 586 AN XY: 726402

African (AFR) AF: 0.0361 AC: 1206 AN: 33446

American (AMR) AF: 0.00137 AC: 61 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52140

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111770

Other (OTH) AF: 0.00187 AC: 113 AN: 60336

GnomAD4 genome AF: 0.00924 AC: 1408 AN: 152302 Hom.: 31 Cov.: 33 AF XY: 0.00866 AC XY: 645 AN XY: 74482

African (AFR) AF: 0.0326 AC: 1353 AN: 41558

American (AMR) AF: 0.00242 AC: 37 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68010

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00371 Hom.: 3

Bravo AF: 0.0108

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.91
Mutation Taster		=99/1	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: rs78964872; hg19: chr14-55605038;