13-39655705-A-AG

Variant names:

• chr13-39655705-A-AG
• rs67765306
• NM_020751.3:c.-17dupG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020751.3(COG6):​c.-17dupG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,579,008 control chromosomes in the GnomAD database, including 133,674 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12707 hom., cov: 0)
  • Exomes 𝑓: 0.41 (120967 hom.)
• Consequence: COG6 NM_020751.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.35
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 13-39655705-A-AG is Benign according to our data. Variant chr13-39655705-A-AG is described in ClinVar as [Likely_benign]. Clinvar id is 193435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.-17dupG		5_prime_UTR_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1
COG6	NR_026745.1	n.84dupG		non_coding_transcript_exon_variant	Exon 1 of 20
COG6	NM_001145079.2	c.-17dupG		5_prime_UTR_variant	Exon 1 of 19		NP_001138551.1
COG6	XM_011535168.2	c.-17dupG		5_prime_UTR_variant	Exon 1 of 20		XP_011533470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.-17dupG		5_prime_UTR_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61199 AN: 152004 Hom.: 12690 Cov.: 0

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.450

GnomAD2 exomes AF: 0.456 AC: 88241 AN: 193390 AF XY: 0.455

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.647

Gnomad ASJ exome AF: 0.470

Gnomad EAS exome AF: 0.437

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.406 AC: 579521 AN: 1426886 Hom.: 120967 Cov.: 40 AF XY: 0.410 AC XY: 289970 AN XY: 706776

African (AFR) AF: 0.355 AC: 11570 AN: 32580

American (AMR) AF: 0.635 AC: 26136 AN: 41180

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 12030 AN: 25540

East Asian (EAS) AF: 0.467 AC: 17583 AN: 37664

South Asian (SAS) AF: 0.546 AC: 44997 AN: 82364

European-Finnish (FIN) AF: 0.366 AC: 18292 AN: 49974

Middle Eastern (MID) AF: 0.521 AC: 2799 AN: 5370

European-Non Finnish (NFE) AF: 0.385 AC: 421388 AN: 1093370

Other (OTH) AF: 0.420 AC: 24726 AN: 58844

GnomAD4 genome AF: 0.403 AC: 61245 AN: 152122 Hom.: 12707 Cov.: 0 AF XY: 0.407 AC XY: 30289 AN XY: 74350

African (AFR) AF: 0.354 AC: 14704 AN: 41522

American (AMR) AF: 0.567 AC: 8670 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1590 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2308 AN: 5134

South Asian (SAS) AF: 0.522 AC: 2515 AN: 4822

European-Finnish (FIN) AF: 0.362 AC: 3833 AN: 10592

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26091 AN: 67968

Other (OTH) AF: 0.455 AC: 963 AN: 2116

Alfa AF: 0.395 Hom.: 2219

Bravo AF: 0.416

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Oct 14, 2014

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital disorder of glycosylation Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 08, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs67765306; hg19: chr13-40229842; COSMIC: COSV62995061; COSMIC: COSV62995061;