Variant 18-334759-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130386.3(COLEC12):c.1799C>T(p.Pro600Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,470,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

COLEC12
NM_130386.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

COLEC12 (HGNC:16016): (collectin subfamily member 12) This gene encodes a member of the C-lectin family, proteins that possess collagen-like sequences and carbohydrate recognition domains. This protein is a scavenger receptor that displays several functions associated with host defense. It can bind to carbohydrate antigens on microorganisms, facilitating their recognition and removal. It also mediates the recognition, internalization, and degradation of oxidatively modified low density lipoprotein by vascular endothelial cells. [provided by RefSeq, May 2018]

COLEC12 links:

COLEC12 (HGNC:):

COLEC12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07212302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLEC12	NM_130386.3 linkuse as main transcript	c.1799C>T	p.Pro600Leu	missense_variant	6/10	ENST00000400256.5	NP_569057.2	Q5KU26
COLEC12	XM_011525741.3 linkuse as main transcript	c.1748C>T	p.Pro583Leu	missense_variant	5/9		XP_011524043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLEC12	ENST00000400256.5 linkuse as main transcript	c.1799C>T	p.Pro600Leu	missense_variant	6/10	1	NM_130386.3	ENSP00000383115.3		Q5KU26
COLEC12	ENST00000582147.1 linkuse as main transcript	n.2007C>T		non_coding_transcript_exon_variant	6/9	5

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000365

AC:

AN:

136992

Hom.:

AF XY:

0.0000271

AC XY:

AN XY:

73802

show subpopulations

Gnomad AFR exome

AF:

0.0000897

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000610

Gnomad NFE exome

AF:

0.0000433

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

136

AN:

1318750

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

644202

show subpopulations

Gnomad4 AFR exome

AF:

0.000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.0000403

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.0000371

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000582

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.1799C>T (p.P600L) alteration is located in exon 6 (coding exon 6) of the COLEC12 gene. This alteration results from a C to T substitution at nucleotide position 1799, causing the proline (P) at amino acid position 600 to be replaced by a leucine (L). 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

0.066

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.037

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.75

M_CAP

Benign

0.0083

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.9

REVEL

Benign

0.075

Sift

Uncertain

0.0040

Sift4G

Benign

0.16

Polyphen

0.43

Vest4

0.054

MVP

0.12

MPC

0.23

ClinPred

0.066

GERP RS

5.4

Varity_R

0.060

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over