Genetic Variant COG7:c.170-13_170-9delTTTTT (chr16-23445969-TAAAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_153603.4(COG7):c.170-13_170-9delTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000954 in 1,362,680 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 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COG7
NM_153603.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00

Publications

0 publications found

Variant links:

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

COG7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.170-13_170-9delTTTTT		intron	N/A	NP_705831.1	A0A0S2Z652

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COG7	ENST00000307149.10	TSL:1 MANE Select	c.170-13_170-9delTTTTT	intron	N/A	ENSP00000305442.5	P83436
COG7	ENST00000941095.1		c.170-13_170-9delTTTTT	intron	N/A	ENSP00000611154.1
COG7	ENST00000916651.1		c.170-13_170-9delTTTTT	intron	N/A	ENSP00000586710.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

129252

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000954

AC:

AN:

1362680

Hom.:

AF XY:

0.0000118

AC XY:

AN XY:

678854

show subpopulations

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

African (AFR)

AF:

0.0000334

AC:

AN:

29972

American (AMR)

AF:

0.00

AC:

AN:

38550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24644

East Asian (EAS)

AF:

0.0000265

AC:

AN:

37724

South Asian (SAS)

AF:

0.00

AC:

AN:

79304

European-Finnish (FIN)

AF:

0.0000241

AC:

AN:

41512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5094

European-Non Finnish (NFE)

AF:

0.00000953

AC:

AN:

1049254

Other (OTH)

AF:

0.00

AC:

AN:

56626

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.244

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

129252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62174

African (AFR)

AF:

0.00

AC:

AN:

34996

American (AMR)

AF:

0.00

AC:

AN:

12622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3108

East Asian (EAS)

AF:

0.00

AC:

AN:

4592

South Asian (SAS)

AF:

0.00

AC:

AN:

4122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59866

Other (OTH)

AF:

0.00

AC:

AN:

1738

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

16-23445969-TAAAAAA-TA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over