Variant 17-73193119-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018714.3(COG1):c.50A>C(p.Asp17Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

COG1
NM_018714.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

COG1 (HGNC:6545): (component of oligomeric golgi complex 1) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. It is thought that this protein is required for steps in the normal medial and trans Golgi-associated processing of glycoconjugates and plays a role in the organization of the Golgi-localized complex. [provided by RefSeq, Jul 2008]

COG1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG1	NM_018714.3 linkuse as main transcript	c.50A>C	p.Asp17Ala	missense_variant	1/14	ENST00000299886.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COG1	ENST00000299886.9 linkuse as main transcript	c.50A>C	p.Asp17Ala	missense_variant	1/14	1	NM_018714.3	P1
COG1	ENST00000438720.7 linkuse as main transcript	c.50A>C	p.Asp17Ala	missense_variant	1/13	1
COG1	ENST00000582587.2 linkuse as main transcript	c.29A>C	p.Asp10Ala	missense_variant, NMD_transcript_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

240202

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000936

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459392

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.50A>C (p.D17A) alteration is located in exon 1 (coding exon 1) of the COG1 gene. This alteration results from a A to C substitution at nucleotide position 50, causing the aspartic acid (D) at amino acid position 17 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Uncertain

0.070

Cadd

Pathogenic

Dann

Benign

0.91

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.67

T;T

M_CAP

Pathogenic

0.62

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

Sift4G

Uncertain

0.016

D;D

Polyphen

0.67

.;P

Vest4

0.70

MutPred

0.79

Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);

MVP

0.51

MPC

1.3

ClinPred

0.78

GERP RS

3.6

Varity_R

0.74

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