13-39776775-T-C

Variant names:

• chr13-39776775-T-C
• rs7993214
• ENST00000416691.6:c.1827-11560T>C

Variant summary

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

The ENST00000416691.6(COG6):​c.1827-11560T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 151,976 control chromosomes in the GnomAD database, including 34,992 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 0.68 (34992 hom., cov: 33)
• Consequence: COG6 ENST00000416691.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 57 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_001145079.2	c.1827-11560T>C		intron_variant	Intron 18 of 18		NP_001138551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000416691.6	c.1827-11560T>C		intron_variant	Intron 18 of 18	1		ENSP00000403733.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102883 AN: 151860 Hom.: 34957 Cov.: 33

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.678 AC: 102977 AN: 151976 Hom.: 34992 Cov.: 33 AF XY: 0.682 AC XY: 50691 AN XY: 74306

African (AFR) AF: 0.666 AC: 27551 AN: 41370

American (AMR) AF: 0.776 AC: 11856 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2705 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3989 AN: 5172

South Asian (SAS) AF: 0.709 AC: 3415 AN: 4820

European-Finnish (FIN) AF: 0.644 AC: 6815 AN: 10588

Middle Eastern (MID) AF: 0.759 AC: 220 AN: 290

European-Non Finnish (NFE) AF: 0.652 AC: 44320 AN: 67962

Other (OTH) AF: 0.688 AC: 1450 AN: 2108

Alfa AF: 0.668 Hom.: 120045

Bravo AF: 0.688

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		-0.42
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: rs7993214; hg19: chr13-40350912;