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), PanelApp Australia, Ambry Genetics, G2P, Orphanet

COG7 links:

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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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG7	NM_153603.4 link	c.170-13_170-9delTTTTT		intron_variant	Intron 1 of 16	ENST00000307149.10	NP_705831.1	P83436A0A0S2Z652
COG7	XM_017023870.2 link	c.-26-13_-26-9delTTTTT		intron_variant	Intron 1 of 16		XP_016879359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG7	ENST00000307149.10 link	c.170-13_170-9delTTTTT		intron_variant	Intron 1 of 16	1	NM_153603.4	ENSP00000305442.5		P83436

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Splicing

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

Publications

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16-23445969-TAAAAAA-TA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over