Genetic Variant CLEC16A:p.Thr16Ala (chr16-10944763-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015226.3(CLEC16A):c.46A>G(p.Thr16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,609,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

CLEC16A
NM_015226.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CLEC16A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034448504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC16A	NM_015226.3 link	c.46A>G	p.Thr16Ala	missense_variant	Exon 1 of 24	ENST00000409790.6	NP_056041.1	Q2KHT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLEC16A	ENST00000409790.6 link	c.46A>G	p.Thr16Ala	missense_variant	Exon 1 of 24	5	NM_015226.3	ENSP00000387122.1	Q2KHT3-1
CLEC16A	ENST00000409552.4 link	c.46A>G	p.Thr16Ala	missense_variant	Exon 1 of 21	1		ENSP00000386495.3	Q2KHT3-2
CLEC16A	ENST00000703130.1 link	c.46A>G	p.Thr16Ala	missense_variant	Exon 1 of 23			ENSP00000515187.1	A0A8V8TR67

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000302

AC:

AN:

232076

AF XY:

0.0000312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000590

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000491

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000391

AC:

AN:

1457486

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

724826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.000112

AC:

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

85594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51450

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

1110882

Other (OTH)

AF:

0.0000166

AC:

AN:

60166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41362

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000585

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000167

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.46A>G (p.T16A) alteration is located in exon 1 (coding exon 1) of the CLEC16A gene. This alteration results from a A to G substitution at nucleotide position 46, causing the threonine (T) at amino acid position 16 to be replaced by an alanine (A). 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

0.058

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.082

T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.15

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;N

PhyloP100

1.7

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.010

N;N

REVEL

Benign

0.080

Sift

Benign

0.35

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;B

Vest4

0.036

MVP

0.099

MPC

0.76

ClinPred

0.044

GERP RS

4.6

PromoterAI

-0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.10

gMVP

0.13

Mutation Taster

=82/18

polymorphism

(source)

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

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chr16-10944763-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over