13-39655769-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020751.3(COG6):c.43G>A(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21741635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG6	NM_020751.3	c.43G>A	p.Gly15Arg	missense_variant	1/19	ENST00000455146.8
COG6	NM_001145079.2	c.43G>A	p.Gly15Arg	missense_variant	1/19
COG6	XM_011535168.2	c.43G>A	p.Gly15Arg	missense_variant	1/20
COG6	NR_026745.1	n.143G>A		non_coding_transcript_exon_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG6	ENST00000455146.8	c.43G>A	p.Gly15Arg	missense_variant	1/19	1	NM_020751.3	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441626 Hom.: 0 Cov.: 41 AF XY: 0.00000280 AC XY: 2 AN XY: 715496

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.43G>A (p.G15R) alteration is located in exon 1 (coding exon 1) of the COG6 gene. This alteration results from a G to A substitution at nucleotide position 43, causing the glycine (G) at amino acid position 15 to be replaced by an arginine (R). 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	Benign	0.32
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	23
Dann	Pathogenic	1.0
Eigen	Benign	0.061
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;M;.
MutationTaster	Benign	0.89	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.93	N;N;.
REVEL	Benign	0.056
Sift	Benign	0.066	T;T;.
Sift4G	Uncertain	0.036	D;D;D
Polyphen		0.78	.;P;.
Vest4		0.31
MutPred		0.33		Gain of catalytic residue at L20 (P = 0.0161);Gain of catalytic residue at L20 (P = 0.0161);Gain of catalytic residue at L20 (P = 0.0161);
MVP		0.17
MPC		0.38
ClinPred		0.95	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-40229906;