chr13-39699572-T-TA

Position:

• chr13-39699572-T-TA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020751.3(COG6):​c.1239dup​(p.Phe414IlefsTer4) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COG6 NM_020751.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.79

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-39699572-T-TA is Pathogenic according to our data. Variant chr13-39699572-T-TA is described in ClinVar as [Pathogenic]. Clinvar id is 493010.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG6	NM_020751.3	c.1239dup	p.Phe414IlefsTer4	frameshift_variant	13/19	ENST00000455146.8
COG6	NM_001145079.2	c.1239dup	p.Phe414IlefsTer4	frameshift_variant	13/19
COG6	XM_011535168.2	c.1239dup	p.Phe414IlefsTer4	frameshift_variant	13/20
COG6	NR_026745.1	n.1404dup		non_coding_transcript_exon_variant	14/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG6	ENST00000455146.8	c.1239dup	p.Phe414IlefsTer4	frameshift_variant	13/19	1	NM_020751.3	P1
COG6	ENST00000416691.5	c.1239dup	p.Phe414IlefsTer4	frameshift_variant	13/19	1
COG6	ENST00000356576.8	c.*1076dup		3_prime_UTR_variant, NMD_transcript_variant	14/20	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

COG6-ongenital disorder of glycosylation Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

Other links and lift over

dbSNP: rs1555277827; hg19: chr13-40273709;