NM_006438.5:c.324A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006438.5(COLEC10):c.324A>G(p.Ile108Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,609,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COLEC10
NM_006438.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.41

Publications

0 publications found

Variant links:

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

COLEC10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065942526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLEC10	NM_006438.5 link	c.324A>G	p.Ile108Met	missense_variant	Exon 4 of 6	ENST00000332843.3	NP_006429.2	Q9Y6Z7A0A024R9J3
COLEC10	NM_001324095.2 link	c.117A>G	p.Ile39Met	missense_variant	Exon 6 of 8		NP_001311024.1	Q9Y6Z7
COLEC10	XM_005250756.4 link	c.117A>G	p.Ile39Met	missense_variant	Exon 4 of 6		XP_005250813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLEC10	ENST00000332843.3 link	c.324A>G	p.Ile108Met	missense_variant	Exon 4 of 6	1	NM_006438.5	ENSP00000332723.2		Q9Y6Z7
COLEC10	ENST00000521788.1 link	n.411A>G		non_coding_transcript_exon_variant	Exon 5 of 7	3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151464

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249588

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457698

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725044

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39494

South Asian (SAS)

AF:

0.00

AC:

AN:

85304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109798

Other (OTH)

AF:

0.00

AC:

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73946

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41180

American (AMR)

AF:

0.00

AC:

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67894

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.324A>G (p.I108M) alteration is located in exon 4 (coding exon 4) of the COLEC10 gene. This alteration results from a A to G substitution at nucleotide position 324, causing the isoleucine (I) at amino acid position 108 to be replaced by a methionine (M). 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

0.069

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.043

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.29

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.36

PhyloP100

-5.4

PrimateAI

Benign

0.43

PROVEAN

Benign

0.19

REVEL

Benign

0.25

Sift

Benign

0.30

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.20

MutPred

0.33

Loss of methylation at K103 (P = 0.0953);

MVP

0.43

MPC

0.047

ClinPred

0.13

GERP RS

-11

Varity_R

0.048

gMVP

0.40

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_006438.5:c.324A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over