16-69339024-T-C

Position:

• chr16-69339024-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. 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

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:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 16-69339024-T-C is Benign according to our data. Variant chr16-69339024-T-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG8	NM_032382.5	c.377+152A>G		intron_variant		ENST00000306875.10	NP_115758.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG8	ENST00000306875.10	c.377+152A>G		intron_variant		1	NM_032382.5	ENSP00000305459.6
ENSG00000260371	ENST00000563634.1	c.3-2312A>G		intron_variant		4		ENSP00000454500.1
ENSG00000259900	ENST00000564737.1	n.466-2312A>G		intron_variant		5		ENSP00000462747.1

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

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.304

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

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.0919

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.310

Alfa AF: 0.314 Hom.: 1563

Bravo AF: 0.306

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

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