12-10015353-G-A

Position:

• chr12-10015353-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001129998.3(CLEC12B):​c.511G>A​(p.Asp171Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CLEC12B NM_001129998.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.655

Genes affected

CLEC12B (HGNC:31966): (C-type lectin domain family 12 member B) Enables protein phosphatase binding activity and signaling receptor inhibitor activity. Involved in natural killer cell inhibitory signaling pathway; negative regulation of natural killer cell mediated cytotoxicity; and negative regulation of signaling receptor activity. Located in external side of plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1221216).
• BP6: Variant 12-10015353-G-A is Benign according to our data. Variant chr12-10015353-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2311290.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC12B	NM_001129998.3	c.511G>A	p.Asp171Asn	missense_variant	4/6	ENST00000338896.11	NP_001123470.1
LOC102724020	NR_169587.1	n.754C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC12B	ENST00000338896.11	c.511G>A	p.Asp171Asn	missense_variant	4/6	1	NM_001129998.3	ENSP00000344563	P1
	ENST00000544225.1	n.669C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461120 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726870

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: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.0048	.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.43	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.041
Sift	Benign	0.64	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.0020	B;B
Vest4		0.15
MutPred		0.50		Loss of ubiquitination at K170 (P = 0.0431);Loss of ubiquitination at K170 (P = 0.0431);
MVP		0.092
MPC		0.074
ClinPred		0.070	T
GERP RS		1.4
Varity_R		0.047
gMVP		0.20

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: chr12-10167952;