Variant chr18-333047-T-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.1913A>T(p.Lys638Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COLEC12
NM_130386.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.449

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:

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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=0.162271).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLEC12	NM_130386.3 linkuse as main transcript	c.1913A>T	p.Lys638Met	missense_variant	7/10	ENST00000400256.5	NP_569057.2
COLEC12	XM_011525741.3 linkuse as main transcript	c.1862A>T	p.Lys621Met	missense_variant	6/9		XP_011524043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLEC12	ENST00000400256.5 linkuse as main transcript	c.1913A>T	p.Lys638Met	missense_variant	7/10	1	NM_130386.3	ENSP00000383115	P1
COLEC12	ENST00000582147.1 linkuse as main transcript	n.3719A>T		non_coding_transcript_exon_variant	6/9	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457276

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.1913A>T (p.K638M) alteration is located in exon 7 (coding exon 7) of the COLEC12 gene. This alteration results from a A to T substitution at nucleotide position 1913, causing the lysine (K) at amino acid position 638 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

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.062

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.69

M_CAP

Benign

0.012

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.080

MutationTaster

Benign

0.92

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.62

REVEL

Benign

0.068

Sift

Benign

0.14

Sift4G

Benign

0.087

Polyphen

0.79

Vest4

0.32

MutPred

0.60

Loss of ubiquitination at K638 (P = 0.0161);

MVP

0.22

MPC

0.31

ClinPred

0.52

GERP RS

1.8

Varity_R

0.20

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over