13-39687612-C-G

Position:

• chr13-39687612-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020751.3(COG6):​c.898C>G​(p.His300Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63

Genes affected

COG6 (HGNC:18621): (component of oligomeric golgi complex 6) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi apparatus. The encoded protein is organized with conserved oligomeric Golgi complex components 5, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

COG6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG6	NM_020751.3	c.898C>G	p.His300Asp	missense_variant	9/19	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.898C>G	p.His300Asp	missense_variant	9/19		NP_001138551.1
COG6	XM_011535168.2	c.898C>G	p.His300Asp	missense_variant	9/20		XP_011533470.1
COG6	NR_026745.1	n.1063C>G		non_coding_transcript_exon_variant	10/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.898C>G	p.His300Asp	missense_variant	9/19	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	.;T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Uncertain	0.42
Sift	Benign	0.10	T;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.96	.;D
Vest4		0.93
MutPred		0.57		Gain of catalytic residue at H300 (P = 0.003);Gain of catalytic residue at H300 (P = 0.003);
MVP		0.67
MPC		0.37
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.76
gMVP		0.70

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

Other links and lift over

dbSNP: rs34555836; hg19: chr13-40261749;