chr16-69339024-T-C

Variant names:

• chr16-69339024-T-C
• rs3759979
• NM_032382.5:c.377+152A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BA1

The NM_032382.5(COG8):​c.377+152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,025,476 control chromosomes in the GnomAD database, including 51,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7466 hom., cov: 33)
  • Exomes 𝑓: 0.31 (44335 hom.)
• Consequence: COG8 NM_032382.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.658
• Publications: 9 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 -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 16-69339024-T-C is Benign according to our data. Variant chr16-69339024-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

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.377+152A>G		intron	N/A	NP_115758.3
	COG8	NM_001379261.1		c.377+152A>G		intron	N/A	NP_001366190.1
	COG8	NM_001379262.1		c.377+152A>G		intron	N/A	NP_001366191.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG8	ENST00000306875.10	TSL:1 MANE Select	c.377+152A>G		intron	N/A	ENSP00000305459.6	Q96MW5
	ENSG00000260371	ENST00000563634.1	TSL:4	c.3-2312A>G		intron	N/A	ENSP00000454500.1	H3BMQ9
	ENSG00000259900	ENST00000564737.1	TSL:5	n.466-2312A>G		intron	N/A	ENSP00000462747.1	J3KT08

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46725 AN: 151948 Hom.: 7443 Cov.: 33

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.311 AC: 272024 AN: 873410 Hom.: 44335 AF XY: 0.314 AC XY: 140289 AN XY: 446306

African (AFR) AF: 0.346 AC: 7267 AN: 20982

American (AMR) AF: 0.206 AC: 5803 AN: 28128

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 5452 AN: 19484

East Asian (EAS) AF: 0.123 AC: 4362 AN: 35584

South Asian (SAS) AF: 0.367 AC: 24064 AN: 65608

European-Finnish (FIN) AF: 0.268 AC: 10983 AN: 40988

Middle Eastern (MID) AF: 0.349 AC: 1514 AN: 4332

European-Non Finnish (NFE) AF: 0.324 AC: 200409 AN: 618216

Other (OTH) AF: 0.304 AC: 12170 AN: 40088

GnomAD4 genome AF: 0.308 AC: 46798 AN: 152066 Hom.: 7466 Cov.: 33 AF XY: 0.305 AC XY: 22639 AN XY: 74336

African (AFR) AF: 0.335 AC: 13901 AN: 41452

American (AMR) AF: 0.266 AC: 4058 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3472

East Asian (EAS) AF: 0.0919 AC: 476 AN: 5178

South Asian (SAS) AF: 0.357 AC: 1722 AN: 4828

European-Finnish (FIN) AF: 0.253 AC: 2680 AN: 10584

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21845 AN: 67960

Other (OTH) AF: 0.310 AC: 656 AN: 2116

Alfa AF: 0.305 Hom.: 2759

Bravo AF: 0.306

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.66
PromoterAI		0.016	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.77		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.77		Position offset: 1

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

Other links and lift over

dbSNP: rs3759979; hg19: chr16-69372927; COSMIC: COSV54742217; COSMIC: COSV54742217;