19-39706627-G-A

Variant names:

• chr19-39706627-G-A
• rs61737337
• NM_020129.3:c.46G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020129.3(LGALS14):​c.46G>A​(p.Val16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,613,986 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. V16L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.016 (69 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (77 hom.)
• Consequence: LGALS14 NM_020129.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003331542).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

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.46G>A	p.Val16Ile	missense	Exon 2 of 4	NP_064514.1	Q8TCE9-1
	LGALS14	NM_203471.2		c.133G>A	p.Val45Ile	missense	Exon 3 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.46G>A	p.Val16Ile	missense	Exon 2 of 4	ENSP00000375905.2	Q8TCE9-1
	LGALS14	ENST00000360675.7	TSL:3	c.133G>A	p.Val45Ile	missense	Exon 3 of 5	ENSP00000353893.2	Q8TCE9-2
	LGALS14	ENST00000601802.1	TSL:5	c.42-551G>A		intron	N/A	ENSP00000471660.1	M0R163

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2412 AN: 152166 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00620 AC: 1558 AN: 251174 AF XY: 0.00563

Gnomad AFR exome AF: 0.0583

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.000979

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00268 AC: 3921 AN: 1461702 Hom.: 77 Cov.: 30 AF XY: 0.00283 AC XY: 2060 AN XY: 727162

African (AFR) AF: 0.0572 AC: 1915 AN: 33464

American (AMR) AF: 0.00329 AC: 147 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26132

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39696

South Asian (SAS) AF: 0.0135 AC: 1168 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00538 AC: 31 AN: 5764

European-Non Finnish (NFE) AF: 0.000223 AC: 248 AN: 1111876

Other (OTH) AF: 0.00593 AC: 358 AN: 60388

GnomAD4 genome AF: 0.0159 AC: 2421 AN: 152284 Hom.: 69 Cov.: 32 AF XY: 0.0165 AC XY: 1226 AN XY: 74458

African (AFR) AF: 0.0527 AC: 2189 AN: 41546

American (AMR) AF: 0.00549 AC: 84 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5180

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4822

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

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

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68030

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.00540 Hom.: 29

Bravo AF: 0.0175

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0515 AC: 227

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00735 AC: 892

Asia WGS AF: 0.0250 AC: 89 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0090
DANN	Benign	0.43
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.035	N
PhyloP100		-1.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.017
Sift	Benign	0.43	T
Sift4G	Benign	1.0	T
Polyphen		0.010	B
Vest4		0.16
MVP		0.20
MPC		0.11
ClinPred		0.0038	T
GERP RS		-1.8
Varity_R		0.077
gMVP		0.22
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs61737337; hg19: chr19-40197267;