Variant chr13-39655769-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_020751.3(COG6):c.43G>A(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COG6
NM_020751.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

Variant links:

Genes affected

COG6 (HGNC:18621): (component of oligomeric golgi complex 6) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi apparatus. The encoded protein is organized with conserved oligomeric Golgi complex components 5, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

COG6 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=0.21741635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COG6	NM_020751.3 linkuse as main transcript	c.43G>A	p.Gly15Arg	missense_variant	1/19	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2 linkuse as main transcript	c.43G>A	p.Gly15Arg	missense_variant	1/19		NP_001138551.1
COG6	XM_011535168.2 linkuse as main transcript	c.43G>A	p.Gly15Arg	missense_variant	1/20		XP_011533470.1
COG6	NR_026745.1 linkuse as main transcript	n.143G>A		non_coding_transcript_exon_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8 linkuse as main transcript	c.43G>A	p.Gly15Arg	missense_variant	1/19	1	NM_020751.3	ENSP00000397441	P1	Q9Y2V7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441626

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

715496

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:

0.0000239

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

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.43G>A (p.G15R) alteration is located in exon 1 (coding exon 1) of the COG6 gene. This alteration results from a G to A substitution at nucleotide position 43, causing the glycine (G) at amino acid position 15 to be replaced by an arginine (R). 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

0.32

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0096

.;T;T

Eigen

Benign

0.061

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;M;.

MutationTaster

Benign

0.89

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.93

N;N;.

REVEL

Benign

0.056

Sift

Benign

0.066

T;T;.

Sift4G

Uncertain

0.036

D;D;D

Polyphen

0.78

.;P;.

Vest4

0.31

MutPred

0.33

Gain of catalytic residue at L20 (P = 0.0161);Gain of catalytic residue at L20 (P = 0.0161);Gain of catalytic residue at L20 (P = 0.0161);

MVP

0.17

MPC

0.38

ClinPred

0.95

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.30

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