Genetic Variant NM_032382.5:c.185G>C (chr16-69339368-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032382.5(COG8):c.185G>C(p.Arg62Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,427,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R62Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

COG8
NM_032382.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.42

Publications

0 publications found

Variant links:

Genes affected

COG8 (HGNC:18623): (component of oligomeric golgi complex 8) This gene encodes a protein that is a component of the conserved oligomeric Golgi (COG) complex, a multiprotein complex that plays a structural role in the Golgi apparatus, and is involved in intracellular membrane trafficking and glycoprotein modification. Mutations in this gene cause congenital disorder of glycosylation, type IIh, a disease that is characterized by under-glycosylated serum proteins, and whose symptoms include severe psychomotor retardation, failure to thrive, seizures, and dairy and wheat product intolerance. [provided by RefSeq, Jul 2008]

COG8 links:

ENSG00000260371 (HGNC:):

ENSG00000260371 links:

NIP7 (HGNC:24328): (nucleolar pre-rRNA processing protein NIP7) Enables RNA binding activity. Predicted to be involved in ribosomal large subunit biogenesis. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NIP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33653334).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032382.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COG8	NM_032382.5	MANE Select	c.185G>C	p.Arg62Pro	missense	Exon 1 of 6	NP_115758.3
COG8	NM_001379261.1		c.185G>C	p.Arg62Pro	missense	Exon 1 of 7	NP_001366190.1
COG8	NM_001379262.1		c.185G>C	p.Arg62Pro	missense	Exon 1 of 6	NP_001366191.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COG8	ENST00000306875.10	TSL:1 MANE Select	c.185G>C	p.Arg62Pro	missense	Exon 1 of 6	ENSP00000305459.6	Q96MW5
ENSG00000260371	ENST00000563634.1	TSL:4	c.3-2656G>C		intron	N/A	ENSP00000454500.1	H3BMQ9
ENSG00000259900	ENST00000564737.1	TSL:5	n.466-2656G>C		intron	N/A	ENSP00000462747.1	J3KT08

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1427786

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708600

show subpopulations

African (AFR)

AF:

0.0000610

AC:

AN:

32768

American (AMR)

AF:

0.00

AC:

AN:

39618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25638

East Asian (EAS)

AF:

0.00

AC:

AN:

37878

South Asian (SAS)

AF:

0.00

AC:

AN:

84120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5546

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1099984

Other (OTH)

AF:

0.00

AC:

AN:

59248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.043

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

2.4

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

REVEL

Benign

0.14

Sift

Benign

0.15

Sift4G

Benign

0.22

Polyphen

0.89

Vest4

0.41

MutPred

0.46

Gain of loop (P = 0.0045)

MVP

0.55

MPC

1.8

ClinPred

0.92

GERP RS

5.2

PromoterAI

-0.0058

Neutral

(source)

Varity_R

0.63

gMVP

0.79

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over