16-10972946-C-G

Variant names:

• chr16-10972946-C-G
• NM_015226.3:c.613C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015226.3(CLEC16A):​c.613C>G​(p.Gln205Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q205P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLEC16A NM_015226.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4002046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC16A	NM_015226.3	c.613C>G	p.Gln205Glu	missense_variant	Exon 7 of 24	ENST00000409790.6	NP_056041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC16A	ENST00000409790.6	c.613C>G	p.Gln205Glu	missense_variant	Exon 7 of 24	5	NM_015226.3	ENSP00000387122.1
CLEC16A	ENST00000409552.4	c.607C>G	p.Gln203Glu	missense_variant	Exon 6 of 21	1		ENSP00000386495.3
CLEC16A	ENST00000703130.1	c.607C>G	p.Gln203Glu	missense_variant	Exon 6 of 23			ENSP00000515187.1
CLEC16A	ENST00000494853.1	n.88C>G		non_coding_transcript_exon_variant	Exon 2 of 8	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.613C>G (p.Q205E) alteration is located in exon 7 (coding exon 7) of the CLEC16A gene. This alteration results from a C to G substitution at nucleotide position 613, causing the glutamine (Q) at amino acid position 205 to be replaced by a glutamic acid (E). 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	0.095
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.072	T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;.
PhyloP100		6.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.16
Sift	Benign	0.63	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.97	D;P
Vest4		0.60
MutPred		0.30		Loss of helix (P = 0.0821);.;
MVP		0.46
MPC		0.86
ClinPred		0.39	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.27

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

Other links and lift over

hg19: chr16-11066803;