chr19-39707209-A-G

Position:

• chr19-39707209-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020129.3(LGALS14):​c.124A>G​(p.Thr42Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGALS14 NM_020129.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19490543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS14	NM_020129.3	c.124A>G	p.Thr42Ala	missense_variant	3/4	ENST00000392052.8	NP_064514.1
LGALS14	NM_203471.2	c.211A>G	p.Thr71Ala	missense_variant	4/5		NP_982297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS14	ENST00000392052.8	c.124A>G	p.Thr42Ala	missense_variant	3/4	1	NM_020129.3	ENSP00000375905.2
LGALS14	ENST00000360675.7	c.211A>G	p.Thr71Ala	missense_variant	4/5	3		ENSP00000353893.2
LGALS14	ENST00000601802.1	c.73A>G	p.Thr25Ala	missense_variant	2/3	5		ENSP00000471660.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.211A>G (p.T71A) alteration is located in exon 4 (coding exon 3) of the LGALS14 gene. This alteration results from a A to G substitution at nucleotide position 211, causing the threonine (T) at amino acid position 71 to be replaced by an alanine (A). 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	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.041
Sift	Uncertain	0.016	D;T
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	D;.
Vest4		0.21
MutPred		0.58		Gain of catalytic residue at T42 (P = 0.0012);.;
MVP		0.27
MPC		0.50
ClinPred		0.38	T
GERP RS		1.1
Varity_R		0.28
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs928696762; hg19: chr19-40197849;