12-9982067-A-T

Position:

• chr12-9982067-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138337.6(CLEC12A):​c.579A>T​(p.Leu193Phe) 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 pathogenic 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: 0.338

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC12A	NM_138337.6	c.579A>T	p.Leu193Phe	missense_variant	5/6	ENST00000304361.9	NP_612210.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC12A	ENST00000304361.9	c.579A>T	p.Leu193Phe	missense_variant	5/6	1	NM_138337.6	ENSP00000302804	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

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

Feb 17, 2024

The c.609A>T (p.L203F) alteration is located in exon 6 (coding exon 6) of the CLEC12A gene. This alteration results from a A to T substitution at nucleotide position 609, causing the leucine (L) at amino acid position 203 to be replaced by a phenylalanine (F). 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	0.32
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;.;.
Eigen	Benign	0.025
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.0	.;M;M;.
MutationTaster	Benign	0.71	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.63
MutPred		0.72		.;Gain of catalytic residue at E196 (P = 0.1165);Gain of catalytic residue at E196 (P = 0.1165);.;
MVP		0.24
MPC		0.12
ClinPred		0.97	D
GERP RS		0.054
Varity_R		0.52
gMVP		0.57

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: chr12-10134666;