rs149163316

Positions:

chr16-23445077-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_153603.4(COG7):c.406G>A(p.Ala136Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000662 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00067 ( 0 hom. )

Consequence

COG7
NM_153603.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.16

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:

Genome browser will be placed here

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;

BP4

Computational evidence support a benign effect (MetaRNN=0.03299275).

BP6

Variant 16-23445077-C-T is Benign according to our data. Variant chr16-23445077-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 318486.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG7	NM_153603.4 linkuse as main transcript	c.406G>A	p.Ala136Thr	missense_variant	3/17	ENST00000307149.10	NP_705831.1	P83436A0A0S2Z652
COG7	XM_017023870.2 linkuse as main transcript	c.211G>A	p.Ala71Thr	missense_variant	3/17		XP_016879359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG7	ENST00000307149.10 linkuse as main transcript	c.406G>A	p.Ala136Thr	missense_variant	3/17	1	NM_153603.4	ENSP00000305442.5		P83436

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000664

AC:

167

AN:

251468

Hom.:

AF XY:

0.000618

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000695

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000666

AC:

974

AN:

1461614

Hom.:

Cov.:

AF XY:

0.000637

AC XY:

463

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00325

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000684

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.000617

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000681

Hom.:

Bravo

AF:

0.000767

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000552

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000948

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

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 28, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jul 06, 2017

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.018

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.6

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.3

REVEL

Benign

0.22

Sift

Benign

0.14

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.56

MVP

0.51

MPC

0.30

ClinPred

0.27

GERP RS

4.6

Varity_R

0.078

gMVP

0.28

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