Variant 16-10972989-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015226.3(CLEC16A):c.656A>C(p.Tyr219Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLEC16A
NM_015226.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC16A	NM_015226.3 link	c.656A>C	p.Tyr219Ser	missense_variant	7/24	ENST00000409790.6	NP_056041.1	Q2KHT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLEC16A	ENST00000409790.6 link	c.656A>C	p.Tyr219Ser	missense_variant	7/24	5	NM_015226.3	ENSP00000387122.1	Q2KHT3-1
CLEC16A	ENST00000409552.4 link	c.650A>C	p.Tyr217Ser	missense_variant	6/21	1		ENSP00000386495.3	Q2KHT3-2
CLEC16A	ENST00000703130.1 link	c.650A>C	p.Tyr217Ser	missense_variant	6/23			ENSP00000515187.1	A0A8V8TR67
CLEC16A	ENST00000494853.1 link	n.131A>C		non_coding_transcript_exon_variant	2/8	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726542

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 04, 2024

The c.656A>C (p.Y219S) alteration is located in exon 7 (coding exon 7) of the CLEC16A gene. This alteration results from a A to C substitution at nucleotide position 656, causing the tyrosine (Y) at amino acid position 219 to be replaced by a serine (S). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.76

D;.

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Benign

-0.30

MutationAssessor

Benign

2.0

M;.

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-8.4

D;D

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.89

MutPred

0.66

Loss of helix (P = 0.0237);.;

MVP

0.69

MPC

2.2

ClinPred

1.0

GERP RS

5.9

Varity_R

0.95

gMVP

0.89

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over