19-39709299-C-A

Variant names:

• chr19-39709299-C-A
• rs570737997
• NM_020129.3:c.406C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020129.3(LGALS14):​c.406C>A​(p.Leu136Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,583,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L136F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: LGALS14 NM_020129.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.20
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007205695).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020129.3. 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
	LGALS14	NM_020129.3	MANE Select	c.406C>A	p.Leu136Ile	missense	Exon 4 of 4	NP_064514.1	Q8TCE9-1
	LGALS14	NM_203471.2		c.493C>A	p.Leu165Ile	missense	Exon 5 of 5	NP_982297.1	Q8TCE9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS14	ENST00000392052.8	TSL:1 MANE Select	c.406C>A	p.Leu136Ile	missense	Exon 4 of 4	ENSP00000375905.2	Q8TCE9-1
	LGALS14	ENST00000360675.7	TSL:3	c.493C>A	p.Leu165Ile	missense	Exon 5 of 5	ENSP00000353893.2	Q8TCE9-2
	LGALS14	ENST00000601802.1	TSL:5	c.355C>A	p.Leu119Ile	missense	Exon 3 of 3	ENSP00000471660.1	M0R163

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000148 AC: 37 AN: 250578 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00202

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000259 AC: 37 AN: 1431116 Hom.: 0 Cov.: 25 AF XY: 0.0000168 AC XY: 12 AN XY: 714022

African (AFR) AF: 0.00 AC: 0 AN: 32776

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25962

East Asian (EAS) AF: 0.000885 AC: 35 AN: 39534

South Asian (SAS) AF: 0.00 AC: 0 AN: 85582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084184

Other (OTH) AF: 0.0000337 AC: 2 AN: 59424

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.000181 AC: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0010
DANN	Benign	0.19
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.00045	T
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	L
PhyloP100		-4.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.018
Sift	Benign	0.068	T
Sift4G	Benign	0.43	T
Polyphen		0.063	B
Vest4		0.14
MutPred		0.36		Gain of catalytic residue at S138 (P = 0.1453)
MVP		0.055
MPC		0.12
ClinPred		0.041	T
GERP RS		-1.8
Varity_R		0.086
gMVP		0.15
Mutation Taster		=98/2	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: rs570737997; hg19: chr19-40199939;