Variant chr13-45479059-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031431.4(COG3):c.376A>G(p.Lys126Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COG3
NM_031431.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.65

Variant links:

Genes affected

COG3 (HGNC:18619): (component of oligomeric golgi complex 3) This gene encodes a component of the conserved oligomeric Golgi (COG) complex which is composed of eight different subunits and is required for normal Golgi morphology and localization. Defects in the COG complex result in multiple deficiencies in protein glycosylation. The protein encoded by this gene is involved in ER-Golgi transport.[provided by RefSeq, Jun 2011]

COG3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COG3	NM_031431.4 linkuse as main transcript	c.376A>G	p.Lys126Glu	missense_variant	3/23	ENST00000349995.10
COG3	XM_047430702.1 linkuse as main transcript	c.376A>G	p.Lys126Glu	missense_variant	3/19
COG3	XR_007063702.1 linkuse as main transcript	n.474A>G		non_coding_transcript_exon_variant	3/14
COG3	XR_429222.5 linkuse as main transcript	n.474A>G		non_coding_transcript_exon_variant	3/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG3	ENST00000349995.10 linkuse as main transcript	c.376A>G	p.Lys126Glu	missense_variant	3/23	1	NM_031431.4	P1	Q96JB2-1
COG3	ENST00000617493.1 linkuse as main transcript	c.376A>G	p.Lys126Glu	missense_variant	3/12	1			Q96JB2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452950

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

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

Jan 10, 2023

The c.376A>G (p.K126E) alteration is located in exon 3 (coding exon 3) of the COG3 gene. This alteration results from a A to G substitution at nucleotide position 376, causing the lysine (K) at amino acid position 126 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.025

T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.93

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.82

N;.

REVEL

Benign

0.21

Sift

Benign

0.67

T;.

Sift4G

Benign

0.95

T;T

Polyphen

0.98

D;B

Vest4

0.81

MutPred

0.47

Loss of ubiquitination at K126 (P = 0.0056);Loss of ubiquitination at K126 (P = 0.0056);

MVP

0.89

MPC

0.38

ClinPred

0.80

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.44

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