NM_015226.3:c.1088G>T

Variant names:

• chr16-11003090-G-T
• rs775920891
• NM_015226.3:c.1088G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015226.3(CLEC16A):​c.1088G>T​(p.Arg363Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,822 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CLEC16A NM_015226.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC16A	NM_015226.3	c.1088G>T	p.Arg363Leu	missense_variant	Exon 11 of 24	ENST00000409790.6	NP_056041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC16A	ENST00000409790.6	c.1088G>T	p.Arg363Leu	missense_variant	Exon 11 of 24	5	NM_015226.3	ENSP00000387122.1
CLEC16A	ENST00000409552.4	c.1082G>T	p.Arg361Leu	missense_variant	Exon 10 of 21	1		ENSP00000386495.3
CLEC16A	ENST00000703130.1	c.1082G>T	p.Arg361Leu	missense_variant	Exon 10 of 23			ENSP00000515187.1
CLEC16A	ENST00000494853.1	n.563G>T		non_coding_transcript_exon_variant	Exon 6 of 8	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459822 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.
Eigen	Benign	0.077
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.21
Sift	Benign	0.086	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.051	B;B
Vest4		0.84
MutPred		0.45		Loss of MoRF binding (P = 0.0017);.;
MVP		0.41
MPC		0.26
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.21
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs775920891; hg19: chr16-11096947;