16-69339196-G-A

Variant names:

• chr16-69339196-G-A
• rs752889737
• NM_032382.5:c.357C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032382.5(COG8):​c.357C>T​(p.Pro119Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P119P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COG8 NM_032382.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=2.05 with no splicing effect.

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.357C>T	p.Pro119Pro	synonymous	Exon 1 of 6	NP_115758.3
	COG8	NM_001379261.1		c.357C>T	p.Pro119Pro	synonymous	Exon 1 of 7	NP_001366190.1
	COG8	NM_001379262.1		c.357C>T	p.Pro119Pro	synonymous	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.357C>T	p.Pro119Pro	synonymous	Exon 1 of 6	ENSP00000305459.6	Q96MW5
	ENSG00000260371	ENST00000563634.1	TSL:4	c.3-2484C>T		intron	N/A	ENSP00000454500.1	H3BMQ9
	ENSG00000259900	ENST00000564737.1	TSL:5	n.466-2484C>T		intron	N/A	ENSP00000462747.1	J3KT08

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		2.1
PromoterAI		0.0057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs752889737; hg19: chr16-69373099;