13-39664907-T-G

Variant names:

• chr13-39664907-T-G
• rs4569133
• NM_020751.3:c.370-189T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020751.3(COG6):​c.370-189T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,006 control chromosomes in the GnomAD database, including 33,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33406 hom., cov: 32)
• Consequence: COG6 NM_020751.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14
• Publications: 8 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-39664907-T-G is Benign according to our data. Variant chr13-39664907-T-G is described in ClinVar as Benign. ClinVar VariationId is 1269067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.370-189T>G		intron_variant	Intron 3 of 18	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.370-189T>G		intron_variant	Intron 3 of 18		NP_001138551.1
COG6	NR_026745.1	n.535-189T>G		intron_variant	Intron 4 of 19
COG6	XM_011535168.2	c.370-189T>G		intron_variant	Intron 3 of 19		XP_011533470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.370-189T>G		intron_variant	Intron 3 of 18	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100344 AN: 151888 Hom.: 33376 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.685

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.661 AC: 100428 AN: 152006 Hom.: 33406 Cov.: 32 AF XY: 0.663 AC XY: 49268 AN XY: 74306

African (AFR) AF: 0.600 AC: 24876 AN: 41468

American (AMR) AF: 0.771 AC: 11780 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2689 AN: 3468

East Asian (EAS) AF: 0.715 AC: 3687 AN: 5158

South Asian (SAS) AF: 0.689 AC: 3328 AN: 4828

European-Finnish (FIN) AF: 0.644 AC: 6799 AN: 10550

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44885 AN: 67940

Other (OTH) AF: 0.687 AC: 1452 AN: 2114

Alfa AF: 0.663 Hom.: 21308

Bravo AF: 0.670

Asia WGS AF: 0.690 AC: 2399 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.63
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4569133; hg19: chr13-40239044;