chr12-8519106-G-C

Position:

• chr12-8519106-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080387.5(CLEC4D):​c.330G>C​(p.Arg110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC4D NM_080387.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0410

Genes affected

CLEC4D (HGNC:14554): (C-type lectin domain family 4 member D) 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. 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]

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=0.05662185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC4D	NM_080387.5	c.330G>C	p.Arg110Ser	missense_variant	4/6	ENST00000299665.3	NP_525126.2
CLEC4D	XM_011520632.3	c.330G>C	p.Arg110Ser	missense_variant	5/7		XP_011518934.1
CLEC4D	XM_047428771.1	c.330G>C	p.Arg110Ser	missense_variant	4/6		XP_047284727.1
CLEC4D	XM_047428772.1	c.330G>C	p.Arg110Ser	missense_variant	4/6		XP_047284728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC4D	ENST00000299665.3	c.330G>C	p.Arg110Ser	missense_variant	4/6	1	NM_080387.5	ENSP00000299665.2
CLEC4D	ENST00000382064.6	c.330G>C	p.Arg110Ser	missense_variant	5/6	3		ENSP00000371496.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.330G>C (p.R110S) alteration is located in exon 4 (coding exon 4) of the CLEC4D gene. This alteration results from a G to C substitution at nucleotide position 330, causing the arginine (R) at amino acid position 110 to be replaced by a serine (S). 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	0.23
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.0055	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.099	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	.;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.016
Sift	Benign	0.14	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.046	.;B
Vest4		0.29
MutPred		0.42		Gain of disorder (P = 0.0509);Gain of disorder (P = 0.0509);
MVP		0.14
MPC		0.044
ClinPred		0.057	T
GERP RS		-1.1
Varity_R		0.31
gMVP		0.40

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: chr12-8671702;