rs35541195

Variant names:

• chr19-39705971-C-T
• rs35541195
• NM_020129.3:c.16-626C>T

Variant summary

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

The NM_203471.2(LGALS14):​c.64C>T​(p.Arg22Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,500 control chromosomes in the GnomAD database, including 11,127 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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: 𝑓 0.094 (825 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10302 hom.)
• Consequence: LGALS14 NM_203471.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 9 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=0.0016011596).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

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.16-626C>T		intron	N/A	NP_064514.1	Q8TCE9-1
	LGALS14	NM_203471.2		c.64C>T	p.Arg22Cys	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.16-626C>T		intron	N/A	ENSP00000375905.2	Q8TCE9-1
	LGALS14	ENST00000360675.7	TSL:3	c.64C>T	p.Arg22Cys	missense	Exon 2 of 5	ENSP00000353893.2	Q8TCE9-2
	LGALS14	ENST00000601802.1	TSL:5	c.42-1207C>T		intron	N/A	ENSP00000471660.1	M0R163

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14323 AN: 152064 Hom.: 825 Cov.: 32

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.0964

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0915 AC: 22758 AN: 248714 AF XY: 0.0912

Gnomad AFR exome AF: 0.0464

Gnomad AMR exome AF: 0.0632

Gnomad ASJ exome AF: 0.0975

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.113 AC: 164918 AN: 1461318 Hom.: 10302 Cov.: 31 AF XY: 0.111 AC XY: 80619 AN XY: 727006

African (AFR) AF: 0.0434 AC: 1453 AN: 33462

American (AMR) AF: 0.0660 AC: 2953 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0966 AC: 2525 AN: 26128

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39688

South Asian (SAS) AF: 0.0314 AC: 2711 AN: 86246

European-Finnish (FIN) AF: 0.163 AC: 8728 AN: 53402

Middle Eastern (MID) AF: 0.0845 AC: 486 AN: 5754

European-Non Finnish (NFE) AF: 0.126 AC: 139939 AN: 1111562

Other (OTH) AF: 0.101 AC: 6119 AN: 60358

GnomAD4 genome AF: 0.0941 AC: 14327 AN: 152182 Hom.: 825 Cov.: 32 AF XY: 0.0919 AC XY: 6841 AN XY: 74412

African (AFR) AF: 0.0477 AC: 1981 AN: 41526

American (AMR) AF: 0.0904 AC: 1382 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 334 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4818

European-Finnish (FIN) AF: 0.161 AC: 1702 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8516 AN: 67988

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.110 Hom.: 2207

Bravo AF: 0.0874

Asia WGS AF: 0.0210 AC: 73 AN: 3478

EpiCase AF: 0.134

EpiControl AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.84
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.38
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.040
Sift	Benign	0.056	T
Sift4G	Uncertain	0.057	T
gMVP		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35541195;

hg19: chr19-40196611;

COSMIC: COSV107475399;