Variant 16-11003159-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015226.3(CLEC16A):c.1157G>A(p.Arg386Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000237 in 1,613,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

CLEC16A
NM_015226.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Variant links:

Genes affected

CLEC16A (HGNC:29013): (C-type lectin domain containing 16A) This gene encodes a member of the C-type lectin domain containing family. Single nucleotide polymorphisms in introns of this gene have been associated with diabetes mellitus, multiple sclerosis and rheumatoid arthritis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

CLEC16A links:

CLEC16A (HGNC:):

CLEC16A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.082845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC16A	NM_015226.3 linkuse as main transcript	c.1157G>A	p.Arg386Gln	missense_variant	11/24	ENST00000409790.6	NP_056041.1	Q2KHT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLEC16A	ENST00000409790.6 linkuse as main transcript	c.1157G>A	p.Arg386Gln	missense_variant	11/24	5	NM_015226.3	ENSP00000387122.1	Q2KHT3-1
CLEC16A	ENST00000409552.4 linkuse as main transcript	c.1151G>A	p.Arg384Gln	missense_variant	10/21	1		ENSP00000386495.3	Q2KHT3-2
CLEC16A	ENST00000703130.1 linkuse as main transcript	c.1151G>A	p.Arg384Gln	missense_variant	10/23			ENSP00000515187.1	A0A8V8TR67
CLEC16A	ENST00000494853.1 linkuse as main transcript	n.632G>A		non_coding_transcript_exon_variant	6/8	3

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

151626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000558

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000954

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000197

AC:

AN:

249104

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.000582

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000418

Gnomad NFE exome

AF:

0.000248

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000234

AC:

342

AN:

1461596

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.000268

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000264

AC:

AN:

151744

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.000556

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000954

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000243

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.000525

AC:

ESP6500EA

AF:

0.000364

AC:

ExAC

AF:

0.000257

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2023

The c.1157G>A (p.R386Q) alteration is located in exon 11 (coding exon 11) of the CLEC16A gene. This alteration results from a G to A substitution at nucleotide position 1157, causing the arginine (R) at amino acid position 386 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.10

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.083

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.092

Sift

Benign

0.16

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.93

P;P

Vest4

0.50

MVP

0.53

MPC

0.29

ClinPred

0.40

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.074

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over