rs10403702

Positions:

• chr19-39657944-T-C

Variant summary

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

The NM_001190441.3(LGALS16):​c.77T>C​(p.Leu26Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,613,958 control chromosomes in the GnomAD database, including 1,931 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.

• Frequency:
  • Genomes: 𝑓 0.063 (1001 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (930 hom.)
• Consequence: LGALS16 NM_001190441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990

Genes affected

LGALS16 (HGNC:40039): (galectin 16) Enables lactose binding activity. Involved in positive regulation of T cell apoptotic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01038757).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS16	NM_001190441.3	c.77T>C	p.Leu26Pro	missense_variant	2/4	ENST00000392051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS16	ENST00000392051.4	c.77T>C	p.Leu26Pro	missense_variant	2/4	1	NM_001190441.3	P1
LGALS16	ENST00000594480.1	c.132T>C	p.Thr44=	synonymous_variant, NMD_transcript_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9632 AN: 152190 Hom.: 998 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0463

GnomAD3 exomes AF: 0.0185 AC: 4652 AN: 251258 Hom.: 424 AF XY: 0.0140 AC XY: 1902 AN XY: 135786

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.00983

Gnomad ASJ exome AF: 0.0504

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.00760 AC: 11105 AN: 1461650 Hom.: 930 Cov.: 31 AF XY: 0.00675 AC XY: 4909 AN XY: 727138

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0492

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000554

Gnomad4 OTH exome AF: 0.0177

GnomAD4 genome AF: 0.0634 AC: 9661 AN: 152308 Hom.: 1001 Cov.: 32 AF XY: 0.0609 AC XY: 4539 AN XY: 74494

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0117 Hom.: 170

Bravo AF: 0.0718

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.0218 AC: 2650

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.12
DANN	Benign	0.039
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00014	N
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	4.1	N
REVEL	Benign	0.058
Sift	Benign	1.0	T
Sift4G	Benign	0.68	T
Vest4		0.033
MPC		0.037
ClinPred		0.00011	T
GERP RS		0.065
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10403702; hg19: chr19-40148584; COSMIC: COSV67425326;