Genetic Variant NM_153603.4:c.170-9delT (chr16-23445969-TA-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_153603.4(COG7):c.170-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 129,158 control chromosomes in the GnomAD database, including 2,493 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.21 ( 2493 hom., cov: 25)

Exomes 𝑓: 0.35 ( 209 hom. )

Failed GnomAD Quality Control

Consequence

COG7
NM_153603.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.490

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 16-23445969-TA-T is Benign according to our data. Variant chr16-23445969-TA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 318492.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}. Variant chr16-23445969-TA-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

27386

AN:

129126

Hom.:

2492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.124

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.200

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.354

AC:

423678

AN:

1196694

Hom.:

209

Cov.:

AF XY:

0.357

AC XY:

212304

AN XY:

595238

show subpopulations

Gnomad4 AFR exome

AF:

0.347

Gnomad4 AMR exome

AF:

0.342

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.385

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.356

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.212

AC:

27399

AN:

129158

Hom.:

2493

Cov.:

AF XY:

0.217

AC XY:

13468

AN XY:

62160

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.204

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

COG7 congenital disorder of glycosylation

Benign:2

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

East Asian population allele frequency is 40.02% (rs775122990 5,448/13,622 alleles, 60 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.1.0, this variant is classified as BENIGN. Following criteria are met: BA1 -

Nov 06, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital disorder of glycosylation

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 31, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over