13-39655660-A-T

Variant names:

• chr13-39655660-A-T
• rs548475910
• ENST00000416691.6:c.-67A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000542266.5(COG6):​n.-67A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000533 in 1,531,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00055 (0 hom.)
• Consequence: COG6 ENST00000542266.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.392
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NR_026745.1	n.34A>T		non_coding_transcript_exon_variant	Exon 1 of 20
COG6	NM_020751.3	c.-67A>T		upstream_gene_variant		ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.-67A>T		upstream_gene_variant			NP_001138551.1
COG6	XM_011535168.2	c.-67A>T		upstream_gene_variant			XP_011533470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.-67A>T		upstream_gene_variant		1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152186 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000422 AC: 63 AN: 149126 AF XY: 0.000399

Gnomad AFR exome AF: 0.000273

Gnomad AMR exome AF: 0.000763

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000645

Gnomad OTH exome AF: 0.00140

GnomAD4 exome AF: 0.000547 AC: 755 AN: 1379600 Hom.: 0 Cov.: 28 AF XY: 0.000535 AC XY: 365 AN XY: 681842

African (AFR) AF: 0.0000640 AC: 2 AN: 31264

American (AMR) AF: 0.000640 AC: 23 AN: 35914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25060

East Asian (EAS) AF: 0.00 AC: 0 AN: 35696

South Asian (SAS) AF: 0.00 AC: 0 AN: 78854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.000652 AC: 693 AN: 1062706

Other (OTH) AF: 0.000645 AC: 37 AN: 57328

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152304 Hom.: 0 Cov.: 34 AF XY: 0.000295 AC XY: 22 AN XY: 74480

African (AFR) AF: 0.000120 AC: 5 AN: 41578

American (AMR) AF: 0.000588 AC: 9 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68016

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000447 Hom.: 0

Bravo AF: 0.000495

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital disorder of glycosylation Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Uncertain:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.9
DANN	Benign	0.77
PhyloP100		-0.39
PromoterAI		-0.033	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs548475910; hg19: chr13-40229797;