Variant 12-10125446-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_197947.3(CLEC7A):c.343G>A(p.Val115Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,496 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CLEC7A
NM_197947.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.217

Variant links:

Genes affected

CLEC7A (HGNC:14558): (C-type lectin domain containing 7A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

CLEC7A links:

CLEC7A (HGNC:):

CLEC7A links:

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ACMG classification

Classification made for transcript

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=0.03227371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC7A	NM_197947.3 linkuse as main transcript	c.343G>A	p.Val115Ile	missense_variant, splice_region_variant	4/6	ENST00000304084.13	NP_922938.1	Q9BXN2-1Q68D78A0A024RAN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC7A	ENST00000304084.13 linkuse as main transcript	c.343G>A	p.Val115Ile	missense_variant, splice_region_variant	4/6	1	NM_197947.3	ENSP00000302569.8		Q9BXN2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000243

AC:

AN:

246786

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

133786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457496

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000677

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2024

The c.343G>A (p.V115I) alteration is located in exon 4 (coding exon 4) of the CLEC7A gene. This alteration results from a G to A substitution at nucleotide position 343, causing the valine (V) at amino acid position 115 to be replaced by an isoleucine (I). 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

0.070

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

DANN

Benign

0.51

DEOGEN2

Benign

0.072

.;.;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.52

T;T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.030

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;.;L;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.33

N;N;N;N;N

REVEL

Benign

0.029

Sift

Benign

0.33

T;T;T;T;T

Sift4G

Benign

0.43

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.16

MutPred

0.28

.;.;.;Loss of catalytic residue at V115 (P = 0.0166);Loss of catalytic residue at V115 (P = 0.0166);

MVP

0.11

MPC

0.025

ClinPred

0.026

GERP RS

-2.7

Varity_R

0.021

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over