NM_032382.5:c.249C>G

Variant names:

• chr16-69339304-G-C
• rs144030835
• NM_032382.5:c.249C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS1

The NM_032382.5(COG8):​c.249C>G​(p.Ala83Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,611,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00057 (0 hom.)
• Consequence: COG8 NM_032382.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 2.21
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 16-69339304-G-C is Benign according to our data. Variant chr16-69339304-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 320318.
• BP7: Synonymous conserved (PhyloP=2.21 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000473 (72/152332) while in subpopulation NFE AF = 0.00075 (51/68026). AF 95% confidence interval is 0.000585. There are 0 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.249C>G	p.Ala83Ala	synonymous	Exon 1 of 6	NP_115758.3
	COG8	NM_001379261.1		c.249C>G	p.Ala83Ala	synonymous	Exon 1 of 7	NP_001366190.1
	COG8	NM_001379262.1		c.249C>G	p.Ala83Ala	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.249C>G	p.Ala83Ala	synonymous	Exon 1 of 6	ENSP00000305459.6	Q96MW5
	ENSG00000260371	ENST00000563634.1	TSL:4	c.3-2592C>G		intron	N/A	ENSP00000454500.1	H3BMQ9
	ENSG00000259900	ENST00000564737.1	TSL:5	n.466-2592C>G		intron	N/A	ENSP00000462747.1	J3KT08

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000383 AC: 92 AN: 240452 AF XY: 0.000385

Gnomad AFR exome AF: 0.000348

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000775

Gnomad OTH exome AF: 0.000337

GnomAD4 exome AF: 0.000567 AC: 827 AN: 1459380 Hom.: 0 Cov.: 31 AF XY: 0.000588 AC XY: 427 AN XY: 726014

African (AFR) AF: 0.000299 AC: 10 AN: 33450

American (AMR) AF: 0.0000224 AC: 1 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51768

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.000713 AC: 792 AN: 1111468

Other (OTH) AF: 0.000332 AC: 20 AN: 60308

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74492

African (AFR) AF: 0.000409 AC: 17 AN: 41584

American (AMR) AF: 0.000131 AC: 2 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68026

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000386 Hom.: 0

Bravo AF: 0.000468

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	COG8-congenital disorder of glycosylation (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		2.2
PromoterAI		-0.11	Neutral
Mutation Taster		=98/2	polymorphism

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: rs144030835; hg19: chr16-69373207;