16-69339401-C-T

Variant names:

• chr16-69339401-C-T
• rs2012408265
• NM_032382.5:c.152G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032382.5(COG8):​c.152G>A​(p.Arg51Gln) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R51W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COG8 NM_032382.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21259767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032382.5. 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
	COG8	NM_032382.5	MANE Select	c.152G>A	p.Arg51Gln	missense	Exon 1 of 6	NP_115758.3
	COG8	NM_001379261.1		c.152G>A	p.Arg51Gln	missense	Exon 1 of 7	NP_001366190.1
	COG8	NM_001379262.1		c.152G>A	p.Arg51Gln	missense	Exon 1 of 6	NP_001366191.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG8	ENST00000306875.10	TSL:1 MANE Select	c.152G>A	p.Arg51Gln	missense	Exon 1 of 6	ENSP00000305459.6	Q96MW5
	ENSG00000260371	ENST00000563634.1	TSL:4	c.3-2689G>A		intron	N/A	ENSP00000454500.1	H3BMQ9
	ENSG00000259900	ENST00000564737.1	TSL:5	n.466-2689G>A		intron	N/A	ENSP00000462747.1	J3KT08

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.25
Eigen_PC	Benign	0.0035
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		3.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.33	N
REVEL	Benign	0.090
Sift	Benign	0.59	T
Sift4G	Benign	0.39	T
Polyphen		0.14	B
Vest4		0.37
MutPred		0.53		Loss of MoRF binding (P = 0.0281)
MVP		0.45
MPC		0.95
ClinPred		0.75	D
GERP RS		5.2
PromoterAI		-0.068	Neutral
Varity_R		0.15
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2012408265; hg19: chr16-69373304;