12-9980721-C-G

Position:

• chr12-9980721-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138337.6(CLEC12A):​c.519C>G​(p.Asn173Lys) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC12A NM_138337.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.754

Genes affected

CLEC12A (HGNC:31713): (C-type lectin domain family 12 member A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. This gene is closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region on chromosome 12p13. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24865738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC12A	NM_138337.6	c.519C>G	p.Asn173Lys	missense_variant	4/6	ENST00000304361.9	NP_612210.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC12A	ENST00000304361.9	c.519C>G	p.Asn173Lys	missense_variant	4/6	1	NM_138337.6	ENSP00000302804	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.549C>G (p.N183K) alteration is located in exon 5 (coding exon 5) of the CLEC12A gene. This alteration results from a C to G substitution at nucleotide position 549, causing the asparagine (N) at amino acid position 183 to be replaced by a lysine (K). 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.14	.;T;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	.;M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.084
Sift	Uncertain	0.021	D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D
Polyphen		0.99	D;D;.;D
Vest4		0.31
MutPred		0.64		.;Loss of ubiquitination at K174 (P = 0.0227);Loss of ubiquitination at K174 (P = 0.0227);.;
MVP		0.048
MPC		0.047
ClinPred		0.53	D
GERP RS		-0.065
Varity_R		0.16
gMVP		0.36

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.

Other links and lift over

hg19: chr12-10133320;