NM_020129.3:c.199T>C

Variant names:

• chr19-39707284-T-C
• rs4830
• NM_020129.3:c.199T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020129.3(LGALS14):​c.199T>C​(p.Cys67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,613,706 control chromosomes in the GnomAD database, including 365,681 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C67Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.68 (36082 hom., cov: 32)
  • Exomes 𝑓: 0.67 (329599 hom.)
• Consequence: LGALS14 NM_020129.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.9925528E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS14	NM_020129.3	c.199T>C	p.Cys67Arg	missense_variant	Exon 3 of 4	ENST00000392052.8	NP_064514.1
LGALS14	NM_203471.2	c.286T>C	p.Cys96Arg	missense_variant	Exon 4 of 5		NP_982297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS14	ENST00000392052.8	c.199T>C	p.Cys67Arg	missense_variant	Exon 3 of 4	1	NM_020129.3	ENSP00000375905.2
LGALS14	ENST00000360675.7	c.286T>C	p.Cys96Arg	missense_variant	Exon 4 of 5	3		ENSP00000353893.2
LGALS14	ENST00000601802.1	c.148T>C	p.Cys50Arg	missense_variant	Exon 2 of 3	5		ENSP00000471660.1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103507 AN: 151986 Hom.: 36035 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.642

GnomAD3 exomes AF: 0.626 AC: 157061 AN: 251074 Hom.: 51812 AF XY: 0.636 AC XY: 86246 AN XY: 135682

Gnomad AFR exome AF: 0.795

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.698

Gnomad EAS exome AF: 0.342

Gnomad SAS exome AF: 0.700

Gnomad FIN exome AF: 0.692

Gnomad NFE exome AF: 0.679

Gnomad OTH exome AF: 0.637

GnomAD4 exome AF: 0.667 AC: 974471 AN: 1461602 Hom.: 329599 Cov.: 46 AF XY: 0.668 AC XY: 486026 AN XY: 727122

Gnomad4 AFR exome AF: 0.801

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.697

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.695

Gnomad4 NFE exome AF: 0.678

Gnomad4 OTH exome AF: 0.661

GnomAD4 genome AF: 0.681 AC: 103597 AN: 152104 Hom.: 36082 Cov.: 32 AF XY: 0.676 AC XY: 50286 AN XY: 74358

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.638

Alfa AF: 0.666 Hom.: 85525

Bravo AF: 0.665

TwinsUK AF: 0.688 AC: 2551

ALSPAC AF: 0.691 AC: 2662

ESP6500AA AF: 0.786 AC: 3465

ESP6500EA AF: 0.674 AC: 5793

ExAC AF: 0.642 AC: 77913

Asia WGS AF: 0.541 AC: 1883 AN: 3478

EpiCase AF: 0.667

EpiControl AF: 0.664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.039
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.39
DANN	Benign	0.10
DEOGEN2	Benign	0.0044	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.000060	N
LIST_S2	Benign	0.19	T;T
MetaRNN	Benign	0.0000020	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	3.3	N;N
REVEL	Benign	0.022
Sift	Benign	0.99	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.046
MPC		0.18
ClinPred		0.00085	T
GERP RS		1.1
Varity_R		0.23
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs4830; hg19: chr19-40197924; COSMIC: COSV62372292;