3-45035684-G-C

Position:

• chr3-45035684-G-C

Variant summary

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

The NM_003278.3(CLEC3B):​c.369G>C​(p.Gln123His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLEC3B NM_003278.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

Genes affected

CLEC3B (HGNC:11891): (C-type lectin domain family 3 member B) Enables calcium ion binding activity; heparin binding activity; and kringle domain binding activity. Involved in bone mineralization and cellular response to transforming growth factor beta stimulus. Located in cytoplasm; extracellular space; and granular component. Part of collagen-containing extracellular matrix. Implicated in osteoarthritis. [provided by Alliance of Genome Resources, Apr 2022]

EXOSC7 (HGNC:28112): (exosome component 7) Predicted to enable 3'-5'-exoribonuclease activity and RNA binding activity. Predicted to be involved in RNA metabolic process. Part of exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

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=0.17527199).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC3B	NM_003278.3	c.369G>C	p.Gln123His	missense_variant	3/3	ENST00000296130.5	NP_003269.2
CLEC3B	NM_001308394.2	c.243G>C	p.Gln81His	missense_variant	3/3		NP_001295323.1
CLEC3B	XM_017007116.2	c.270G>C	p.Gln90His	missense_variant	2/2		XP_016862605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC3B	ENST00000296130.5	c.369G>C	p.Gln123His	missense_variant	3/3	1	NM_003278.3	ENSP00000296130	P1
CLEC3B	ENST00000428034.1	c.243G>C	p.Gln81His	missense_variant	3/3	2		ENSP00000396013
EXOSC7	ENST00000481405.1	n.386G>C		non_coding_transcript_exon_variant	3/3	3
CLEC3B	ENST00000490386.1	n.321G>C		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

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

Sep 27, 2021

The c.369G>C (p.Q123H) alteration is located in exon 3 (coding exon 3) of the CLEC3B gene. This alteration results from a G to C substitution at nucleotide position 369, causing the glutamine (Q) at amino acid position 123 to be replaced by a histidine (H). 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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.088
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.060
Sift	Benign	0.11	T;T
Sift4G	Benign	0.082	T;T
Polyphen		0.012	B;.
Vest4		0.069
MutPred		0.32		Gain of catalytic residue at N127 (P = 0.1534);.;
MVP		0.46
MPC		0.63
ClinPred		0.68	D
GERP RS		2.6
Varity_R		0.36
gMVP		0.39

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: chr3-45077176;