16-23445969-TAAAAAA-TAAAAAAAA

Variant names:

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

Variant summary

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

The NM_153603.4(COG7):​c.170-10_170-9dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000498 in 1,488,844 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000023 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: COG7 NM_153603.4 intron
• Clinical Significance: Not reported in ClinVar
• 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.

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_170-9dupTT		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.170-9_170-8insTT		intron	N/A	ENSP00000305442.5	P83436
	COG7	ENST00000941095.1		c.170-9_170-8insTT		intron	N/A	ENSP00000611154.1
	COG7	ENST00000916651.1		c.170-9_170-8insTT		intron	N/A	ENSP00000586710.1

Frequencies

GnomAD3 genomes AF: 0.0000232 AC: 3 AN: 129252 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000167

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00141 AC: 215 AN: 152462 AF XY: 0.00139

Gnomad AFR exome AF: 0.00187

Gnomad AMR exome AF: 0.00109

Gnomad ASJ exome AF: 0.00132

Gnomad EAS exome AF: 0.00131

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00147

Gnomad OTH exome AF: 0.00104

GnomAD4 exome AF: 0.000544 AC: 739 AN: 1359592 Hom.: 0 Cov.: 0 AF XY: 0.000540 AC XY: 366 AN XY: 677384

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

African (AFR) AF: 0.00107 AC: 32 AN: 29912

American (AMR) AF: 0.00148 AC: 57 AN: 38502

Ashkenazi Jewish (ASJ) AF: 0.000814 AC: 20 AN: 24578

East Asian (EAS) AF: 0.000265 AC: 10 AN: 37694

South Asian (SAS) AF: 0.000619 AC: 49 AN: 79144

European-Finnish (FIN) AF: 0.000458 AC: 19 AN: 41466

Middle Eastern (MID) AF: 0.000197 AC: 1 AN: 5086

European-Non Finnish (NFE) AF: 0.000501 AC: 524 AN: 1046710

Other (OTH) AF: 0.000478 AC: 27 AN: 56500

⚠️ 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: 0.0000232 AC: 3 AN: 129252 Hom.: 0 Cov.: 25 AF XY: 0.0000322 AC XY: 2 AN XY: 62174

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

African (AFR) AF: 0.0000286 AC: 1 AN: 34996

American (AMR) AF: 0.00 AC: 0 AN: 12622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3108

East Asian (EAS) AF: 0.00 AC: 0 AN: 4592

South Asian (SAS) AF: 0.00 AC: 0 AN: 4122

European-Finnish (FIN) AF: 0.000140 AC: 1 AN: 7128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.0000167 AC: 1 AN: 59864

Other (OTH) AF: 0.00 AC: 0 AN: 1738

⚠️ 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: 0.00144 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs71379679; hg19: chr16-23457290;