chr16-10944763-A-T

Variant names:

• chr16-10944763-A-T
• rs756014800
• NM_015226.3:c.46A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015226.3(CLEC16A):​c.46A>T​(p.Thr16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T16A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC16A NM_015226.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 1 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: 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=0.029432178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC16A	NM_015226.3	c.46A>T	p.Thr16Ser	missense_variant	Exon 1 of 24	ENST00000409790.6	NP_056041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC16A	ENST00000409790.6	c.46A>T	p.Thr16Ser	missense_variant	Exon 1 of 24	5	NM_015226.3	ENSP00000387122.1
CLEC16A	ENST00000409552.4	c.46A>T	p.Thr16Ser	missense_variant	Exon 1 of 21	1		ENSP00000386495.3
CLEC16A	ENST00000703130.1	c.46A>T	p.Thr16Ser	missense_variant	Exon 1 of 23			ENSP00000515187.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.61
DEOGEN2	Benign	0.074	T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.036	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.029	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N
PhyloP100		1.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.25	N;N
REVEL	Benign	0.060
Sift	Benign	1.0	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0	B;B
Vest4		0.049
MutPred		0.16		Gain of disorder (P = 0.0488);Gain of disorder (P = 0.0488);
MVP		0.16
MPC		0.70
ClinPred		0.15	T
GERP RS		4.6
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.094
gMVP		0.091

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

dbSNP: rs756014800; hg19: chr16-11038620;