19-39709282-T-C

Variant names:

• chr19-39709282-T-C
• NM_020129.3:c.389T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020129.3(LGALS14):​c.389T>C​(p.Ile130Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LGALS14 NM_020129.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.205

Genes affected

LGALS14 (HGNC:30054): (galectin 14) This gene is predominantly expressed in placenta. The encoded protein belongs to the galectin (galaptin/S-lectin) family. The members of galectin family contain one or two carbohydrate recognition domains, which can bind beta-galactoside. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS14	NM_020129.3	c.389T>C	p.Ile130Thr	missense_variant	Exon 4 of 4	ENST00000392052.8	NP_064514.1
LGALS14	NM_203471.2	c.476T>C	p.Ile159Thr	missense_variant	Exon 5 of 5		NP_982297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS14	ENST00000392052.8	c.389T>C	p.Ile130Thr	missense_variant	Exon 4 of 4	1	NM_020129.3	ENSP00000375905.2
LGALS14	ENST00000360675.7	c.476T>C	p.Ile159Thr	missense_variant	Exon 5 of 5	3		ENSP00000353893.2
LGALS14	ENST00000601802.1	c.338T>C	p.Ile113Thr	missense_variant	Exon 3 of 3	5		ENSP00000471660.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456108 Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2 AN XY: 724856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.476T>C (p.I159T) alteration is located in exon 5 (coding exon 4) of the LGALS14 gene. This alteration results from a T to C substitution at nucleotide position 476, causing the isoleucine (I) at amino acid position 159 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.065	T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.086
Sift	Benign	0.13	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.55	P;.
Vest4		0.42
MutPred		0.87		Loss of stability (P = 0.0335);.;
MVP		0.081
MPC		0.30
ClinPred		0.39	T
GERP RS		0.75
Varity_R		0.37
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-40199922;