19-39705972-G-T

Variant names:

• chr19-39705972-G-T
• rs567124884
• NM_020129.3:c.16-625G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203471.2(LGALS14):​c.65G>T​(p.Arg22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. R22H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LGALS14 NM_203471.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041619867).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203471.2. 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.16-625G>T		intron	N/A	NP_064514.1	Q8TCE9-1
	LGALS14	NM_203471.2		c.65G>T	p.Arg22Leu	missense	Exon 2 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.16-625G>T		intron	N/A	ENSP00000375905.2	Q8TCE9-1
	LGALS14	ENST00000360675.7	TSL:3	c.65G>T	p.Arg22Leu	missense	Exon 2 of 5	ENSP00000353893.2	Q8TCE9-2
	LGALS14	ENST00000601802.1	TSL:5	c.42-1206G>T		intron	N/A	ENSP00000471660.1	M0R163

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461612 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727124

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111826

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.090
DANN	Benign	0.36
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.6
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.00053	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.98	T
PhyloP100		-3.0
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.010
Sift	Benign	0.27	T
Sift4G	Benign	0.40	T
Vest4		0.098
MutPred		0.61		Loss of MoRF binding (P = 0.0591)
MVP		0.16
MPC		0.13
ClinPred		0.094	T
GERP RS		-1.8
gMVP		0.52
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs567124884; hg19: chr19-40196612;