13-39679963-AT-ATT

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The NM_020751.3(COG6):c.624-3dupT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,389,362 control chromosomes in the GnomAD database, including 35,440 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5858 hom., cov: 21)

Exomes 𝑓: 0.23 ( 29582 hom. )

Consequence

COG6
NM_020751.3 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.428

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

COG6-congenital disorder of glycosylation
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COG6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.035967577 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.4, offset of 0 (no position change), new splice context is: atcattaattttttttttAGttt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BP6

Variant 13-39679963-A-AT is Benign according to our data. Variant chr13-39679963-A-AT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 198581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020751.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COG6	NM_020751.3	MANE Select	c.624-3dupT	splice_acceptor intron	N/A	NP_065802.1
COG6	NM_001145079.2		c.624-3dupT	splice_acceptor intron	N/A	NP_001138551.1
COG6	NR_026745.1		n.789-3dupT	splice_acceptor intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COG6	ENST00000455146.8	TSL:1 MANE Select	c.624-3dupT	splice_acceptor intron	N/A	ENSP00000397441.2
COG6	ENST00000416691.6	TSL:1	c.624-3dupT	splice_acceptor intron	N/A	ENSP00000403733.1
COG6	ENST00000356576.8	TSL:1	n.*461-3dupT	splice_acceptor intron	N/A	ENSP00000348983.4

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41422

AN:

151418

Hom.:

5851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.240

AC:

55295

AN:

230006

AF XY:

0.242

show subpopulations

Gnomad AFR exome

AF:

0.361

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.289

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.231

AC:

285939

AN:

1237828

Hom.:

29582

Cov.:

AF XY:

0.232

AC XY:

144852

AN XY:

625694

show subpopulations

African (AFR)

AF:

0.341

AC:

9605

AN:

28162

American (AMR)

AF:

0.146

AC:

6340

AN:

43486

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

4570

AN:

24552

East Asian (EAS)

AF:

0.287

AC:

10823

AN:

37726

South Asian (SAS)

AF:

0.233

AC:

18233

AN:

78230

European-Finnish (FIN)

AF:

0.271

AC:

14184

AN:

52414

Middle Eastern (MID)

AF:

0.203

AC:

1048

AN:

5158

European-Non Finnish (NFE)

AF:

0.228

AC:

208974

AN:

915626

Other (OTH)

AF:

0.232

AC:

12162

AN:

52474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9636

19272

28907

38543

48179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6800

13600

20400

27200

34000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.274

AC:

41454

AN:

151534

Hom.:

5858

Cov.:

AF XY:

0.274

AC XY:

20261

AN XY:

74040

show subpopulations

African (AFR)

AF:

0.362

AC:

14979

AN:

41354

American (AMR)

AF:

0.185

AC:

2820

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

667

AN:

3466

East Asian (EAS)

AF:

0.280

AC:

1444

AN:

5160

South Asian (SAS)

AF:

0.263

AC:

1263

AN:

4808

European-Finnish (FIN)

AF:

0.278

AC:

2900

AN:

10436

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.245

AC:

16582

AN:

67784

Other (OTH)

AF:

0.265

AC:

557

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1485

2969

4454

5938

7423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.146

Hom.:

308

Bravo

AF:

0.267

Asia WGS

AF:

0.278

AC:

955

AN:

3432

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 12, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Congenital disorder of glycosylation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Jul 21, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over