13-39699514-A-G

Position:

chr13-39699514-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020751.3(COG6):c.1180A>G(p.Asn394Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000523 in 1,561,924 control chromosomes in the GnomAD database, including 2 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

COG6
NM_020751.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 8.85

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:

COG6 (HGNC:):

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=0.009499133).

BP6

Variant 13-39699514-A-G is Benign according to our data. Variant chr13-39699514-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 235506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00305 (463/151974) while in subpopulation AFR AF= 0.0108 (450/41516). AF 95% confidence interval is 0.01. There are 2 homozygotes in gnomad4. There are 196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG6	NM_020751.3 linkuse as main transcript	c.1180A>G	p.Asn394Asp	missense_variant	13/19	ENST00000455146.8	NP_065802.1	Q9Y2V7-1A0A024RDW5
COG6	NM_001145079.2 linkuse as main transcript	c.1180A>G	p.Asn394Asp	missense_variant	13/19		NP_001138551.1	Q9Y2V7-2A0A140VJG7
COG6	XM_011535168.2 linkuse as main transcript	c.1180A>G	p.Asn394Asp	missense_variant	13/20		XP_011533470.1
COG6	NR_026745.1 linkuse as main transcript	n.1345A>G		non_coding_transcript_exon_variant	14/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COG6	ENST00000455146.8 linkuse as main transcript	c.1180A>G	p.Asn394Asp	missense_variant	13/19	1	NM_020751.3	ENSP00000397441.2	Q9Y2V7-1
COG6	ENST00000416691.5 linkuse as main transcript	c.1180A>G	p.Asn394Asp	missense_variant	13/19	1		ENSP00000403733.1	Q9Y2V7-2
COG6	ENST00000356576.8 linkuse as main transcript	n.*1017A>G		non_coding_transcript_exon_variant	14/20	1		ENSP00000348983.4	Q9Y2V7-4
COG6	ENST00000356576.8 linkuse as main transcript	n.*1017A>G		3_prime_UTR_variant	14/20	1		ENSP00000348983.4	Q9Y2V7-4

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

463

AN:

151856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000723

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:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000630

AC:

157

AN:

249312

Hom.:

AF XY:

0.000445

AC XY:

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.00949

Gnomad AMR exome

AF:

0.0000877

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000251

AC:

354

AN:

1409950

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

148

AN XY:

704710

show subpopulations

Gnomad4 AFR exome

AF:

0.00950

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000188

Gnomad4 OTH exome

AF:

0.000667

GnomAD4 genome

AF:

0.00305

AC:

463

AN:

151974

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

196

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.000722

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000470

Hom.:

Bravo

AF:

0.00325

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000899

AC:

109

Asia WGS

AF:

0.000579

AC:

AN:

3468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 11, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	COG6: BS1 -

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 18, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Feb 18, 2022	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 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. -

COG6-congenital disorder of glycosylation

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0037

.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.090

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0095

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.68

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.12

Sift

Benign

0.64

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0

.;B

Vest4

0.52

MVP

0.35

MPC

0.059

ClinPred

0.068

GERP RS

5.3

Varity_R

0.24

gMVP

0.29

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