19-39707284-T-C

Position:

• chr19-39707284-T-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 same amino acid change has been previously reported as Likely benignin UniProt.

• 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/exons	MANE	Protein	UniProt
LGALS14	NM_020129.3	c.199T>C	p.Cys67Arg	missense_variant	3/4	ENST00000392052.8	NP_064514.1
LGALS14	NM_203471.2	c.286T>C	p.Cys96Arg	missense_variant	4/5		NP_982297.1

Ensembl

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