13-39655742-G-C

Variant names:

• chr13-39655742-G-C
• rs751060043
• NM_020751.3:c.16G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020751.3(COG6):​c.16G>C​(p.Gly6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• COG6-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
• hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089598894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.16G>C	p.Gly6Arg	missense_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.16G>C	p.Gly6Arg	missense_variant	Exon 1 of 19		NP_001138551.1
COG6	XM_011535168.2	c.16G>C	p.Gly6Arg	missense_variant	Exon 1 of 20		XP_011533470.1
COG6	NR_026745.1	n.116G>C		non_coding_transcript_exon_variant	Exon 1 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.16G>C	p.Gly6Arg	missense_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000463 AC: 1 AN: 216094 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000608

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000837 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0080	.;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.090	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;.
PhyloP100		3.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.050	N;N;.
REVEL	Benign	0.043
Sift	Benign	0.062	T;T;.
Sift4G	Benign	0.46	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.29
MutPred		0.39		Gain of relative solvent accessibility (P = 0.0483);Gain of relative solvent accessibility (P = 0.0483);Gain of relative solvent accessibility (P = 0.0483);
MVP		0.085
MPC		0.061
ClinPred		0.55	D
GERP RS		3.8
PromoterAI		0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.060
gMVP		0.28
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs751060043; hg19: chr13-40229879;