8-119067295-C-T

Variant names:

• chr8-119067295-C-T
• rs373479493
• NM_006438.5:c.14C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006438.5(COLEC10):​c.14C>T​(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COLEC10 NM_006438.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• 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

ENSG00000254278 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10212624).

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.14C>T	p.Ala5Val	missense	Exon 1 of 6	NP_006429.2	Q9Y6Z7
	COLEC10	NM_001324095.2		c.-59-22385C>T		intron	N/A	NP_001311024.1
	LOC101927513	NR_134297.1		n.1109+379G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC10	ENST00000332843.3	TSL:1 MANE Select	c.14C>T	p.Ala5Val	missense	Exon 1 of 6	ENSP00000332723.2	Q9Y6Z7
	ENSG00000254278	ENST00000518362.2	TSL:1	n.1109+379G>A		intron	N/A
	COLEC10	ENST00000892377.1		c.14C>T	p.Ala5Val	missense	Exon 1 of 8	ENSP00000562436.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461612 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727118

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111830

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.15
Sift	Benign	0.18	T
Sift4G	Benign	0.26	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.40		Loss of helix (P = 0.0093)
MVP		0.46
MPC		0.046
ClinPred		0.090	T
GERP RS		3.9
PromoterAI		0.037	Neutral
Varity_R		0.031
gMVP		0.64
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs373479493; hg19: chr8-120079534;