16-69331089-G-C

Variant names:

• chr16-69331089-G-C
• NM_032382.5:c.1589C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032382.5(COG8):​c.1589C>G​(p.Pro530Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COG8 NM_032382.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.46

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]

ENSG00000272617 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32879055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG8	NM_032382.5	c.1589C>G	p.Pro530Arg	missense_variant	Exon 5 of 6	ENST00000306875.10	NP_115758.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG8	ENST00000306875.10	c.1589C>G	p.Pro530Arg	missense_variant	Exon 5 of 6	1	NM_032382.5	ENSP00000305459.6
ENSG00000272617	ENST00000562949.1	c.352-1910C>G		intron_variant	Intron 1 of 1	3		ENSP00000457718.1
COG8	ENST00000562595.5	c.548+4237C>G		intron_variant	Intron 3 of 3	5		ENSP00000456705.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jun 25, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1589C>G (p.P530R) alteration is located in exon 5 (coding exon 5) of the COG8 gene. This alteration results from a C to G substitution at nucleotide position 1589, causing the proline (P) at amino acid position 530 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.7	D;.
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;.
Polyphen		0.53	.;P
MutPred		0.35		.;Loss of glycosylation at P530 (P = 0.0243);
MVP		0.67
MPC		0.15
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.20
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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: chr16-69364992;