8-119067391-A-C

Position:

• chr8-119067391-A-C

Variant summary

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

The NM_006438.5(COLEC10):​c.110A>C​(p.Glu37Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COLEC10 NM_006438.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

Genes affected

COLEC10 (HGNC:2220): (collectin subfamily member 10) This gene encodes a member of the C-lectin family, proteins that possess collagen-like sequences and carbohydrate recognition domains. The other members of this family are secreted proteins and bind to carbohydrate antigens on microorganisms facilitating their recognition and removal. This gene product is a cytosolic protein, a characteristic that suggests that it may have different biological functions than other C-lectins. [provided by RefSeq, Jul 2008]

ENSG00000254278 (HGNC:):

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=0.25208437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLEC10	NM_006438.5	c.110A>C	p.Glu37Ala	missense_variant	1/6	ENST00000332843.3	NP_006429.2
COLEC10	NM_001324095.2	c.-59-22289A>C		intron_variant			NP_001311024.1
COLEC10	XM_005250756.4	c.-59-22289A>C		intron_variant			XP_005250813.1
LOC101927513	NR_134297.1	n.1109+283T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLEC10	ENST00000332843.3	c.110A>C	p.Glu37Ala	missense_variant	1/6	1	NM_006438.5	ENSP00000332723.2
ENSG00000254278	ENST00000518362.1	n.1109+283T>G		intron_variant		1
COLEC10	ENST00000521788.1	n.236-22289A>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Nov 29, 2023

The c.110A>C (p.E37A) alteration is located in exon 1 (coding exon 1) of the COLEC10 gene. This alteration results from a A to C substitution at nucleotide position 110, causing the glutamic acid (E) at amino acid position 37 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.033	D
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.058	T
Polyphen		0.048	B
Vest4		0.28
MutPred		0.36		Gain of relative solvent accessibility (P = 0.0249);
MVP		0.86
MPC		0.064
ClinPred		0.62	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs918263036; hg19: chr8-120079630;