chr12-7730863-A-C

Variant names:

• chr12-7730863-A-C
• NM_001371390.1:c.431T>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001371390.1(CLEC4C):​c.431T>G​(p.Leu144Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CLEC4C NM_001371390.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.941

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC4C	NM_001371390.1	c.431T>G	p.Leu144Arg	missense_variant	Exon 5 of 6	ENST00000360345.8	NP_001358319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC4C	ENST00000360345.8	c.431T>G	p.Leu144Arg	missense_variant	Exon 5 of 6	1	NM_001371390.1	ENSP00000353500.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458164 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 725610

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.;.;T;.;.
Eigen	Uncertain	0.40
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.92	.;.;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.94	D;D;D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	4.5	H;.;.;H;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.7	D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;.;.
Vest4		0.83
MutPred		0.86		Gain of methylation at L144 (P = 0.0087);.;.;Gain of methylation at L144 (P = 0.0087);.;.;
MVP		0.72
MPC		1.4
ClinPred		0.99	D
GERP RS		1.9
Varity_R		0.82
gMVP		0.93

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: chr12-7883459;