chr13-39655754-G-A

Position:

chr13-39655754-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020751.3(COG6):c.28G>A(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,591,734 control chromosomes in the GnomAD database, including 140,263 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15026 hom., cov: 34)

Exomes 𝑓: 0.41 ( 125237 hom. )

Consequence

COG6
NM_020751.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.101

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4144059E-5).

BP6

Variant 13-39655754-G-A is Benign according to our data. Variant chr13-39655754-G-A is described in ClinVar as [Benign]. Clinvar id is 193436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-39655754-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COG6	NM_020751.3 linkuse as main transcript	c.28G>A	p.Ala10Thr	missense_variant	1/19	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2 linkuse as main transcript	c.28G>A	p.Ala10Thr	missense_variant	1/19		NP_001138551.1
COG6	XM_011535168.2 linkuse as main transcript	c.28G>A	p.Ala10Thr	missense_variant	1/20		XP_011533470.1
COG6	NR_026745.1 linkuse as main transcript	n.128G>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.28G>A	p.Ala10Thr	missense_variant	1/19	1	NM_020751.3	ENSP00000397441	P1	Q9Y2V7-1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66684

AN:

152068

Hom.:

15008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.475

GnomAD3 exomes

AF:

0.475

AC:

100290

AN:

210934

Hom.:

24581

AF XY:

0.471

AC XY:

54169

AN XY:

114932

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.661

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.449

Gnomad SAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.375

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.463

GnomAD4 exome

AF:

0.412

AC:

592562

AN:

1439548

Hom.:

125237

Cov.:

AF XY:

0.415

AC XY:

296728

AN XY:

714206

show subpopulations

Gnomad4 AFR exome

AF:

0.474

Gnomad4 AMR exome

AF:

0.649

Gnomad4 ASJ exome

AF:

0.474

Gnomad4 EAS exome

AF:

0.474

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.370

Gnomad4 NFE exome

AF:

0.387

Gnomad4 OTH exome

AF:

0.430

GnomAD4 genome

AF:

0.439

AC:

66745

AN:

152186

Hom.:

15026

Cov.:

AF XY:

0.442

AC XY:

32894

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.476

Gnomad4 AMR

AF:

0.584

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.362

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.480

Alfa

AF:

0.402

Hom.:

21465

Bravo

AF:

0.456

TwinsUK

AF:

0.388

AC:

1438

ALSPAC

AF:

0.388

AC:

1494

ESP6500AA

AF:

0.494

AC:

2156

ESP6500EA

AF:

0.409

AC:

3484

ExAC

AF:

0.441

AC:

52046

Asia WGS

AF:

0.514

AC:

1786

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 14, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

COG6-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

COG6-congenital disorder of glycosylation;C3809160:Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0080

.;T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.85

T;T;T

MetaRNN

Benign

0.000014

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

0.070

N;N;.

REVEL

Benign

0.029

Sift

Benign

0.18

T;T;.

Sift4G

Benign

0.36

T;T;D

Polyphen

0.0030

.;B;.

Vest4

0.099

MPC

0.054

ClinPred

0.034

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.36

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