rs146054602

Variant names:

• chr13-39677522-A-C
• rs146054602
• NM_020751.3:c.483A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-39677522-A-C
• chr13-39677522-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020751.3(COG6):​c.483A>C​(p.Gln161His) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0910
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.895

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.483A>C	p.Gln161His	missense_variant	Exon 5 of 19	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.483A>C	p.Gln161His	missense_variant	Exon 5 of 19		NP_001138551.1
COG6	XM_011535168.2	c.483A>C	p.Gln161His	missense_variant	Exon 5 of 20		XP_011533470.1
COG6	NR_026745.1	n.648A>C		non_coding_transcript_exon_variant	Exon 6 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.483A>C	p.Gln161His	missense_variant	Exon 5 of 19	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jun 22, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	.;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.1	M;M
PhyloP100		-0.091
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.4	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	.;D
Vest4		0.82
MutPred		0.79		Gain of catalytic residue at K159 (P = 0.0018);Gain of catalytic residue at K159 (P = 0.0018);
MVP		0.39
MPC		0.34
ClinPred		0.99	D
GERP RS		-2.2
Varity_R		0.34
gMVP		0.57
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs146054602; hg19: chr13-40251659;