chr16-23445969-TA-T

Variant names:

• chr16-23445969-TA-T
• rs71379679
• NM_153603.4:c.170-9delT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_153603.4(COG7):​c.170-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 129,158 control chromosomes in the GnomAD database, including 2,493 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (2493 hom., cov: 25)
  • Exomes 𝑓: 0.35 (209 hom.)
  • Failed GnomAD Quality Control
• Consequence: COG7 NM_153603.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.490
• Publications: 2 publications found

Genes affected

COG7 (HGNC:18622): (component of oligomeric golgi complex 7) The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010]

COG7 Gene-Disease associations (from GenCC):

• COG7-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 16-23445969-TA-T is Benign according to our data. Variant chr16-23445969-TA-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 318492.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153603.4. 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
	COG7	NM_153603.4	MANE Select	c.170-9delT		intron	N/A	NP_705831.1	A0A0S2Z652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG7	ENST00000307149.10	TSL:1 MANE Select	c.170-9delT		intron	N/A	ENSP00000305442.5	P83436
	COG7	ENST00000941095.1		c.170-9delT		intron	N/A	ENSP00000611154.1
	COG7	ENST00000916651.1		c.170-9delT		intron	N/A	ENSP00000586710.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 27386 AN: 129126 Hom.: 2492 Cov.: 25

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.200

GnomAD2 exomes AF: 0.404 AC: 61621 AN: 152462 AF XY: 0.403

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.426

Gnomad EAS exome AF: 0.410

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.411

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.354 AC: 423678 AN: 1196694 Hom.: 209 Cov.: 0 AF XY: 0.357 AC XY: 212304 AN XY: 595238

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.347 AC: 9302 AN: 26808

American (AMR) AF: 0.342 AC: 11975 AN: 34976

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 7661 AN: 21618

East Asian (EAS) AF: 0.385 AC: 13387 AN: 34760

South Asian (SAS) AF: 0.380 AC: 26699 AN: 70214

European-Finnish (FIN) AF: 0.356 AC: 13719 AN: 38522

Middle Eastern (MID) AF: 0.345 AC: 1591 AN: 4618

European-Non Finnish (NFE) AF: 0.351 AC: 321425 AN: 914990

Other (OTH) AF: 0.357 AC: 17919 AN: 50188

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.212 AC: 27399 AN: 129158 Hom.: 2493 Cov.: 25 AF XY: 0.217 AC XY: 13468 AN XY: 62160

African (AFR) AF: 0.219 AC: 7663 AN: 35040

American (AMR) AF: 0.181 AC: 2281 AN: 12624

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 519 AN: 3104

East Asian (EAS) AF: 0.305 AC: 1397 AN: 4582

South Asian (SAS) AF: 0.261 AC: 1069 AN: 4096

European-Finnish (FIN) AF: 0.293 AC: 2082 AN: 7116

Middle Eastern (MID) AF: 0.135 AC: 33 AN: 244

European-Non Finnish (NFE) AF: 0.198 AC: 11860 AN: 59790

Other (OTH) AF: 0.204 AC: 356 AN: 1748

Alfa AF: 0.167 Hom.: 4

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	COG7 congenital disorder of glycosylation (2)
-	1	-	Congenital disorder of glycosylation (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs71379679; hg19: chr16-23457290;