Genetic Variant NM_153603.4:c.170-11_170-9dupTTT (chr16-23445969-T-TAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_153603.4(COG7):c.170-11_170-9dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000811 in 1,491,906 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 0.000054 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

COG7
NM_153603.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.490

Publications

2 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG7	NM_153603.4 link	c.170-11_170-9dupTTT		intron_variant	Intron 1 of 16	ENST00000307149.10	NP_705831.1	P83436A0A0S2Z652
COG7	XM_017023870.2 link	c.-26-11_-26-9dupTTT		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.170-9_170-8insTTT		intron_variant	Intron 1 of 16	1	NM_153603.4	ENSP00000305442.5		P83436

Frequencies

GnomAD3 genomes

AF:

0.0000542

AC:

AN:

129242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000792

Gnomad ASJ

AF:

0.000322

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000140

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000501

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000837

AC:

114

AN:

1362664

Hom.:

Cov.:

AF XY:

0.0000722

AC XY:

AN XY:

678842

show subpopulations

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

African (AFR)

AF:

0.000133

AC:

AN:

29968

American (AMR)

AF:

0.000389

AC:

AN:

38540

Ashkenazi Jewish (ASJ)

AF:

0.000284

AC:

AN:

24636

East Asian (EAS)

AF:

0.00

AC:

AN:

37722

South Asian (SAS)

AF:

0.000164

AC:

AN:

79308

European-Finnish (FIN)

AF:

0.000120

AC:

AN:

41508

Middle Eastern (MID)

AF:

0.000196

AC:

AN:

5094

European-Non Finnish (NFE)

AF:

0.0000610

AC:

AN:

1049252

Other (OTH)

AF:

0.0000883

AC:

AN:

56636

⚠️ 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: 0.314

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

AF:

0.0000542

AC:

AN:

129242

Hom.:

Cov.:

AF XY:

0.0000322

AC XY:

AN XY:

62170

show subpopulations

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

African (AFR)

AF:

0.0000286

AC:

AN:

34992

American (AMR)

AF:

0.0000792

AC:

AN:

12622

Ashkenazi Jewish (ASJ)

AF:

0.000322

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:

0.000140

AC:

AN:

7128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0000501

AC:

AN:

59860

Other (OTH)

AF:

0.00

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.49

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over