12-7729681-C-G

Variant names:

• chr12-7729681-C-G
• rs1193664214
• NM_001371390.1:c.557G>C

Variant summary

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

The NM_001371390.1(CLEC4C):​c.557G>C​(p.Arg186Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLEC4C NM_001371390.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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]

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=0.094680965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC4C	NM_001371390.1	c.557G>C	p.Arg186Pro	missense_variant	Exon 6 of 6	ENST00000360345.8	NP_001358319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC4C	ENST00000360345.8	c.557G>C	p.Arg186Pro	missense_variant	Exon 6 of 6	1	NM_001371390.1	ENSP00000353500.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461176 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726984

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: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.5
DANN	Benign	0.89
DEOGEN2	Benign	0.036	T;.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.27	.;.;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.095	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;.;.;L
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.070
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.35	B;B;B;B
Vest4		0.15
MutPred		0.60		Loss of catalytic residue at R186 (P = 0.0936);.;.;Loss of catalytic residue at R186 (P = 0.0936);
MVP		0.14
MPC		0.69
ClinPred		0.050	T
GERP RS		-1.2
Varity_R		0.65
gMVP		0.80

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: rs1193664214; hg19: chr12-7882277;