Genetic Variant COLEC10:p.Pro93Ser (chr8-119091205-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006438.5(COLEC10):c.277C>T(p.Pro93Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (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: 4.36

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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLEC10	NM_006438.5 link	c.277C>T	p.Pro93Ser	missense_variant	Exon 3 of 6	ENST00000332843.3	NP_006429.2	Q9Y6Z7A0A024R9J3
COLEC10	NM_001324095.2 link	c.70C>T	p.Pro24Ser	missense_variant	Exon 5 of 8		NP_001311024.1	Q9Y6Z7
COLEC10	XM_005250756.4 link	c.70C>T	p.Pro24Ser	missense_variant	Exon 3 of 6		XP_005250813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLEC10	ENST00000332843.3 link	c.277C>T	p.Pro93Ser	missense_variant	Exon 3 of 6	1	NM_006438.5	ENSP00000332723.2		Q9Y6Z7
COLEC10	ENST00000521788.1 link	n.364C>T		non_coding_transcript_exon_variant	Exon 4 of 7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459434

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726024

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.00

AC:

AN:

85926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110596

Other (OTH)

AF:

0.00

AC:

AN:

60280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 05, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.277C>T (p.P93S) alteration is located in exon 3 (coding exon 3) of the COLEC10 gene. This alteration results from a C to T substitution at nucleotide position 277, causing the proline (P) at amino acid position 93 to be replaced by a serine (S). 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

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.70

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.087

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.63

MutationAssessor

Benign

1.8

PhyloP100

4.4

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.55

Sift

Uncertain

0.0020

Sift4G

Benign

0.097

Polyphen

1.0

Vest4

0.72

MutPred

0.40

Gain of phosphorylation at P93 (P = 0.0169);

MVP

0.98

MPC

0.29

ClinPred

0.99

GERP RS

6.0

Varity_R

0.39

gMVP

0.36

Mutation Taster

=43/57

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over