dbSNP rs1297158508: COG8:p.Arg62Pro (chr16-69339368-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG8	NM_032382.5 link	c.185G>C	p.Arg62Pro	missense_variant	Exon 1 of 6	ENST00000306875.10	NP_115758.3	Q96MW5A0A024R6Z6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COG8	ENST00000306875.10 link	c.185G>C	p.Arg62Pro	missense_variant	Exon 1 of 6	1	NM_032382.5	ENSP00000305459.6	Q96MW5B4DYU2
ENSG00000260371	ENST00000563634.1 link	c.3-2656G>C		intron_variant	Intron 1 of 2	4		ENSP00000454500.1	H3BMQ9
ENSG00000259900	ENST00000564737.1 link	n.466-2656G>C		intron_variant	Intron 3 of 4	5		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

Gnomad4 AFR exome

AF:

0.0000610

Gnomad4 AMR exome

AF:

0.00

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:

9.09e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

.;T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

.;.;N

REVEL

Benign

0.14

Sift

Benign

0.15

.;.;T

Sift4G

Benign

0.22

.;.;T

Polyphen

0.89

P;P;.

Vest4

0.41

MutPred

0.46

.;Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);

MVP

0.55

MPC

1.8

ClinPred

0.92

GERP RS

5.2

Varity_R

0.63

gMVP

0.79

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over