dbSNP rs10403702: LGALS16:p.Leu26Pro (chr19-39657944-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 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.

Frequency

Genomes: 𝑓 0.063 ( 1001 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 930 hom. )

Consequence

LGALS16
NM_001190441.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.990

Publications

8 publications found

Variant links:

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]

LGALS16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LGALS16	NM_001190441.3 link	c.77T>C	p.Leu26Pro	missense_variant	Exon 2 of 4	ENST00000392051.4	NP_001177370.2	A8MUM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS16	ENST00000392051.4 link	c.77T>C	p.Leu26Pro	missense_variant	Exon 2 of 4	1	NM_001190441.3	ENSP00000375904.2		A8MUM7
LGALS16	ENST00000594480.1 link	n.132T>C		non_coding_transcript_exon_variant	Exon 2 of 4	3		ENSP00000471564.1		M0R108

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9632

AN:

152190

Hom.:

998

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0185

AC:

4652

AN:

251258

AF XY:

0.0140

show subpopulations

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 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.:

AF XY:

0.00675

AC XY:

4909

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.226

AC:

7549

AN:

33476

American (AMR)

AF:

0.0108

AC:

484

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0492

AC:

1287

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.000394

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53250

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000554

AC:

616

AN:

1111968

Other (OTH)

AF:

0.0177

AC:

1069

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

523

1046

1570

2093

2616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0634

AC:

9661

AN:

152308

Hom.:

1001

Cov.:

AF XY:

0.0609

AC XY:

4539

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.216

AC:

8964

AN:

41540

American (AMR)

AF:

0.0221

AC:

339

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0516

AC:

179

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000827

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00103

AC:

AN:

68024

Other (OTH)

AF:

0.0458

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

386

773

1159

1546

1932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0255

Hom.:

656

Bravo

AF:

0.0718

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.0218

AC:

2650

Asia WGS

AF:

0.0150

AC:

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

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.12

(source)

DANN

Benign

0.039

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00014

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.92

PhyloP100

-0.99

PrimateAI

Benign

0.33

PROVEAN

Benign

4.1

REVEL

Benign

0.058

Sift

Benign

1.0

Sift4G

Benign

0.68

Vest4

0.033

MPC

0.037

ClinPred

0.00011

GERP RS

0.065

gMVP

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over