16-69339225-A-ACGCCTCCACGT

Variant names:

• chr16-69339225-A-ACGCCTCCACGT
• NM_032382.5:c.317_327dupACGTGGAGGCG

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_032382.5(COG8):​c.317_327dupACGTGGAGGCG​(p.Ser110ThrfsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COG8 NM_032382.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.78

Genes affected

COG8 (HGNC:18623): (component of oligomeric golgi complex 8) This gene encodes a protein that is a component of the conserved oligomeric Golgi (COG) complex, a multiprotein complex that plays a structural role in the Golgi apparatus, and is involved in intracellular membrane trafficking and glycoprotein modification. Mutations in this gene cause congenital disorder of glycosylation, type IIh, a disease that is characterized by under-glycosylated serum proteins, and whose symptoms include severe psychomotor retardation, failure to thrive, seizures, and dairy and wheat product intolerance. [provided by RefSeq, Jul 2008]

ENSG00000260371 (HGNC:):

NIP7 (HGNC:24328): (nucleolar pre-rRNA processing protein NIP7) Enables RNA binding activity. Predicted to be involved in ribosomal large subunit biogenesis. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 12 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 16-69339225-A-ACGCCTCCACGT is Pathogenic according to our data. Variant chr16-69339225-A-ACGCCTCCACGT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3767116.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG8	NM_032382.5	c.317_327dupACGTGGAGGCG	p.Ser110ThrfsTer24	frameshift_variant	Exon 1 of 6	ENST00000306875.10	NP_115758.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG8	ENST00000306875.10	c.317_327dupACGTGGAGGCG	p.Ser110ThrfsTer24	frameshift_variant	Exon 1 of 6	1	NM_032382.5	ENSP00000305459.6
ENSG00000260371	ENST00000563634.1	c.3-2524_3-2514dupACGTGGAGGCG		intron_variant	Intron 1 of 2	4		ENSP00000454500.1
ENSG00000259900	ENST00000564737.1	n.466-2524_466-2514dupACGTGGAGGCG		intron_variant	Intron 3 of 4	5		ENSP00000462747.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

COG8-congenital disorder of glycosylation Pathogenic:1

-

Juno Genomics, Hangzhou Juno Genomics, Inc

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PM2_Supporting+PVS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-69373128;