Variant 12-7730810-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371390.1(CLEC4C):c.484A>G(p.Asn162Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CLEC4C
NM_001371390.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.522

Variant links:

Genes affected

CLEC4C (HGNC:13258): (C-type lectin domain family 4 member C) 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 signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in dendritic cell function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

CLEC4C links:

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ACMG classification

Classification made for transcript

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=0.11756623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC4C	NM_001371390.1 linkuse as main transcript	c.484A>G	p.Asn162Asp	missense_variant	5/6	ENST00000360345.8	NP_001358319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC4C	ENST00000360345.8 linkuse as main transcript	c.484A>G	p.Asn162Asp	missense_variant	5/6	1	NM_001371390.1	ENSP00000353500.3		Q8WTT0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714456

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.21e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 30, 2023

The c.484A>G (p.N162D) alteration is located in exon 6 (coding exon 5) of the CLEC4C gene. This alteration results from a A to G substitution at nucleotide position 484, causing the asparagine (N) at amino acid position 162 to be replaced by an aspartic acid (D). 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

0.090

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.8

DANN

Benign

0.84

DEOGEN2

Benign

0.037

T;.;.;T;.;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.56

.;.;T;T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.;L;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D

REVEL

Benign

0.012

Sift

Benign

0.21

T;T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

0.92

P;B;B;P;.;.

Vest4

0.12

MutPred

0.52

Gain of phosphorylation at Y161 (P = 0.1081);.;.;Gain of phosphorylation at Y161 (P = 0.1081);.;.;

MVP

0.51

MPC

0.93

ClinPred

0.068

GERP RS

0.70

Varity_R

0.28

gMVP

0.47

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

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