12-9997262-A-G

Position:

• chr12-9997262-A-G

Variant summary

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

The NM_016509.4(CLEC1B):​c.181T>C​(p.Tyr61His) 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. 15/21 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: CLEC1B NM_016509.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.712

Genes affected

CLEC1B (HGNC:24356): (C-type lectin domain family 1 member B) Natural killer (NK) cells express multiple calcium-dependent (C-type) lectin-like receptors, such as CD94 (KLRD1; MIM 602894) and NKG2D (KLRC4; MIM 602893), that interact with major histocompatibility complex class I molecules and either inhibit or activate cytotoxicity and cytokine secretion. CLEC2 is a C-type lectin-like receptor expressed in myeloid cells and NK cells (Colonna et al., 2000 [PubMed 10671229]).[supplied by OMIM, Jan 2011]

CLEC12A (HGNC:):

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=0.080405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC1B	NM_016509.4	c.181T>C	p.Tyr61His	missense_variant	3/6	ENST00000298527.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC1B	ENST00000298527.11	c.181T>C	p.Tyr61His	missense_variant	3/6	1	NM_016509.4	P1
CLEC1B	ENST00000348658.4	c.82T>C	p.Tyr28His	missense_variant	2/5	1
CLEC1B	ENST00000428126.6	c.82T>C	p.Tyr28His	missense_variant	4/7	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 12, 2022

The c.181T>C (p.Y61H) alteration is located in exon 3 (coding exon 3) of the CLEC1B gene. This alteration results from a T to C substitution at nucleotide position 181, causing the tyrosine (Y) at amino acid position 61 to be replaced by a histidine (H). 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	0.071
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.9
DANN	Benign	0.63
DEOGEN2	Benign	0.076	.;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.62	.;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	.;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.012
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.23	B;B;B
Vest4		0.20
MutPred		0.43		.;Gain of disorder (P = 0.0216);.;
MVP		0.20
MPC		0.055
ClinPred		0.17	T
GERP RS		-0.17
Varity_R		0.032
gMVP		0.35

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: rs1591852060; hg19: chr12-10149861;