Genetic Variant NM_153603.4:c.170-9dupT (chr16-23445969-T-TA) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1

The NM_153603.4(COG7):c.170-9dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,460,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 25)

Exomes 𝑓: 0.039 ( 0 hom. )

Consequence

COG7
NM_153603.4 intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 16-23445969-T-TA is Benign according to our data. Variant chr16-23445969-T-TA is described in ClinVar as [Benign]. Clinvar id is 3041322.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00197 (255/129254) while in subpopulation NFE AF= 0.00287 (172/59852). AF 95% confidence interval is 0.00252. There are 0 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

255

AN:

129224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000800

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00166

Gnomad ASJ

AF:

0.000644

Gnomad EAS

AF:

0.000436

Gnomad SAS

AF:

0.00218

Gnomad FIN

AF:

0.00253

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00287

Gnomad OTH

AF:

0.00173

GnomAD4 exome

AF:

0.0393

AC:

52288

AN:

1330852

Hom.:

Cov.:

AF XY:

0.0377

AC XY:

25017

AN XY:

663272

show subpopulations

Gnomad4 AFR exome

AF:

0.0341

Gnomad4 AMR exome

AF:

0.0280

Gnomad4 ASJ exome

AF:

0.0370

Gnomad4 EAS exome

AF:

0.0200

Gnomad4 SAS exome

AF:

0.0249

Gnomad4 FIN exome

AF:

0.0242

Gnomad4 NFE exome

AF:

0.0425

Gnomad4 OTH exome

AF:

0.0366

GnomAD4 genome

AF:

0.00197

AC:

255

AN:

129254

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

137

AN XY:

62204

show subpopulations

Gnomad4 AFR

AF:

0.000799

Gnomad4 AMR

AF:

0.00166

Gnomad4 ASJ

AF:

0.000644

Gnomad4 EAS

AF:

0.000436

Gnomad4 SAS

AF:

0.00219

Gnomad4 FIN

AF:

0.00253

Gnomad4 NFE

AF:

0.00287

Gnomad4 OTH

AF:

0.00171

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

COG7-related disorder

Benign:1

Jun 15, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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