chr16-23445969-TAA-T

Variant names:

• chr16-23445969-TAA-T
• rs71379679
• NM_153603.4:c.170-10_170-9delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_153603.4(COG7):​c.170-10_170-9delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,393,646 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 25)
  • Exomes 𝑓: 0.040 (1 hom.)
• Consequence: COG7 NM_153603.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Variant has high frequency in the EAS (0.0718) population. However there is too low homozygotes in high coverage region: (expected more than 464, got 1).
• BP6: Variant 16-23445969-TAA-T is Benign according to our data. Variant chr16-23445969-TAA-T is described in ClinVar as Benign. ClinVar VariationId is 701826.Status of the report is criteria_provided_single_submitter, 1 stars.

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.170-10_170-9delTT		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.170-10_170-9delTT		intron	N/A	ENSP00000305442.5	P83436
	COG7	ENST00000941095.1		c.170-10_170-9delTT		intron	N/A	ENSP00000611154.1
	COG7	ENST00000916651.1		c.170-10_170-9delTT		intron	N/A	ENSP00000586710.1

Frequencies

GnomAD3 genomes AF: 0.000744 AC: 96 AN: 129118 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000952

Gnomad ASJ AF: 0.000644

Gnomad EAS AF: 0.000436

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000569

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0868 AC: 13227 AN: 152462 AF XY: 0.0896

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.0749

Gnomad ASJ exome AF: 0.0509

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.0891

Gnomad OTH exome AF: 0.0773

GnomAD4 exome AF: 0.0402 AC: 50802 AN: 1264500 Hom.: 1 AF XY: 0.0410 AC XY: 25867 AN XY: 630538

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

African (AFR) AF: 0.0464 AC: 1293 AN: 27844

American (AMR) AF: 0.0625 AC: 2231 AN: 35722

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 1002 AN: 22852

East Asian (EAS) AF: 0.0742 AC: 2603 AN: 35088

South Asian (SAS) AF: 0.0456 AC: 3380 AN: 74152

European-Finnish (FIN) AF: 0.0651 AC: 2525 AN: 38784

Middle Eastern (MID) AF: 0.0461 AC: 221 AN: 4796

European-Non Finnish (NFE) AF: 0.0362 AC: 35172 AN: 972682

Other (OTH) AF: 0.0452 AC: 2375 AN: 52580

⚠️ 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: 0.000743 AC: 96 AN: 129146 Hom.: 0 Cov.: 25 AF XY: 0.000885 AC XY: 55 AN XY: 62140

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

African (AFR) AF: 0.000285 AC: 10 AN: 35056

American (AMR) AF: 0.000951 AC: 12 AN: 12618

Ashkenazi Jewish (ASJ) AF: 0.000644 AC: 2 AN: 3108

East Asian (EAS) AF: 0.000436 AC: 2 AN: 4586

South Asian (SAS) AF: 0.00 AC: 0 AN: 4102

European-Finnish (FIN) AF: 0.00508 AC: 36 AN: 7090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.000569 AC: 34 AN: 59782

Other (OTH) AF: 0.00 AC: 0 AN: 1746

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0301 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	COG7 congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=100/0	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: rs71379679; hg19: chr16-23457290;