18-335075-C-G

Variant summary

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

The NM_130386.3(COLEC12):ā€‹c.1483G>Cā€‹(p.Glu495Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000745 in 1,611,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00019 ( 0 hom., cov: 32)
Exomes š‘“: 0.000062 ( 0 hom. )

Consequence

COLEC12
NM_130386.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00
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]

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=0.12056044).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COLEC12NM_130386.3 linkuse as main transcriptc.1483G>C p.Glu495Gln missense_variant 6/10 ENST00000400256.5 NP_569057.2
COLEC12XM_011525741.3 linkuse as main transcriptc.1432G>C p.Glu478Gln missense_variant 5/9 XP_011524043.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COLEC12ENST00000400256.5 linkuse as main transcriptc.1483G>C p.Glu495Gln missense_variant 6/101 NM_130386.3 ENSP00000383115 P1
COLEC12ENST00000582147.1 linkuse as main transcriptn.1691G>C non_coding_transcript_exon_variant 6/95

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
151952
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000532
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000774
AC:
19
AN:
245420
Hom.:
0
AF XY:
0.0000299
AC XY:
4
AN XY:
133740
show subpopulations
Gnomad AFR exome
AF:
0.000395
Gnomad AMR exome
AF:
0.000177
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000453
Gnomad OTH exome
AF:
0.000335
GnomAD4 exome
AF:
0.0000624
AC:
91
AN:
1459060
Hom.:
0
Cov.:
36
AF XY:
0.0000606
AC XY:
44
AN XY:
725920
show subpopulations
Gnomad4 AFR exome
AF:
0.000541
Gnomad4 AMR exome
AF:
0.000249
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:
0.0000405
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000191
AC:
29
AN:
151952
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74206
show subpopulations
Gnomad4 AFR
AF:
0.000532
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000158
Hom.:
0
Bravo
AF:
0.000261
ESP6500AA
AF:
0.000457
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000660
AC:
8

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 submitterclinical testingAmbry GeneticsAug 16, 2022The c.1483G>C (p.E495Q) alteration is located in exon 6 (coding exon 6) of the COLEC12 gene. This alteration results from a G to C substitution at nucleotide position 1483, causing the glutamic acid (E) at amino acid position 495 to be replaced by a glutamine (Q). 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
-0.54
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.023
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.70
N
MutationTaster
Benign
0.97
D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.075
Sift
Benign
0.24
T
Sift4G
Benign
0.47
T
Polyphen
0.16
B
Vest4
0.27
MVP
0.17
MPC
0.23
ClinPred
0.064
T
GERP RS
5.5
Varity_R
0.25
gMVP
0.55

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.

Other links and lift over

dbSNP: rs376978607; hg19: chr18-335075; API