8-119102365-G-A

Variant names:

• chr8-119102365-G-A
• NM_006438.5:c.310G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2 PM5 PP3_Strong

The NM_006438.5(COLEC10):​c.310G>A​(p.Gly104Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G104V) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COLEC10 NM_006438.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32
• Publications: 0 publications found

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]

COLEC10 Gene-Disease associations (from GenCC):

• 3MC syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: G2P
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr8-119102366-G-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 4081283.Status of the report is criteria_provided_single_submitter, 1 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.991

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC10	NM_006438.5	MANE Select	c.310G>A	p.Gly104Ser	missense	Exon 4 of 6	NP_006429.2	Q9Y6Z7
	COLEC10	NM_001324095.2		c.103G>A	p.Gly35Ser	missense	Exon 6 of 8	NP_001311024.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC10	ENST00000332843.3	TSL:1 MANE Select	c.310G>A	p.Gly104Ser	missense	Exon 4 of 6	ENSP00000332723.2	Q9Y6Z7
	COLEC10	ENST00000892374.1		c.307G>A	p.Gly103Ser	missense	Exon 4 of 6	ENSP00000562433.1
	COLEC10	ENST00000892376.1		c.310G>A	p.Gly104Ser	missense	Exon 4 of 6	ENSP00000562435.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	3MC syndrome 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		5.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.97
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.91		Gain of phosphorylation at G104 (P = 0.0218)
MVP		0.93
MPC		0.32
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.81
gMVP		0.96
Mutation Taster		=35/65	disease causing

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

Other links and lift over

hg19: chr8-120114604; COSMIC: COSV60522781;