13-39763239-C-T

Variant names:

• chr13-39763239-C-T
• rs7337585
• ENST00000416691.6:c.1827-25096C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145079.2(COG6):​c.1827-25096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,198 control chromosomes in the GnomAD database, including 13,419 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13419 hom., cov: 32)
• Consequence: COG6 NM_001145079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 3 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145079.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	NM_001145079.2		c.1827-25096C>T		intron	N/A	NP_001138551.1	A0A140VJG7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	ENST00000416691.6	TSL:1	c.1827-25096C>T		intron	N/A	ENSP00000403733.1	Q9Y2V7-2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 62812 AN: 151078 Hom.: 13402 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.416 AC: 62860 AN: 151198 Hom.: 13419 Cov.: 32 AF XY: 0.421 AC XY: 31083 AN XY: 73864

African (AFR) AF: 0.387 AC: 16005 AN: 41392

American (AMR) AF: 0.565 AC: 8603 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1620 AN: 3454

East Asian (EAS) AF: 0.487 AC: 2511 AN: 5158

South Asian (SAS) AF: 0.550 AC: 2641 AN: 4802

European-Finnish (FIN) AF: 0.361 AC: 3775 AN: 10466

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26213 AN: 67392

Other (OTH) AF: 0.454 AC: 957 AN: 2108

Alfa AF: 0.213 Hom.: 404

Bravo AF: 0.429

Asia WGS AF: 0.535 AC: 1855 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.28
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7337585; hg19: chr13-40337376;