rs4514547

Variant names:

• chr13-39664762-C-T
• rs4514547
• NM_020751.3:c.370-334C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020751.3(COG6):​c.370-334C>T 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 152,120 control chromosomes in the GnomAD database, including 33,470 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33470 hom., cov: 33)
• Consequence: COG6 NM_020751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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.370-334C>T		intron_variant	Intron 3 of 18	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.370-334C>T		intron_variant	Intron 3 of 18		NP_001138551.1
COG6	NR_026745.1	n.535-334C>T		intron_variant	Intron 4 of 19
COG6	XM_011535168.2	c.370-334C>T		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.370-334C>T		intron_variant	Intron 3 of 18	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100485 AN: 152002 Hom.: 33440 Cov.: 33

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.645

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: 100569 AN: 152120 Hom.: 33470 Cov.: 33 AF XY: 0.663 AC XY: 49346 AN XY: 74378

African (AFR) AF: 0.601 AC: 24938 AN: 41474

American (AMR) AF: 0.771 AC: 11799 AN: 15298

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

East Asian (EAS) AF: 0.714 AC: 3694 AN: 5172

South Asian (SAS) AF: 0.689 AC: 3324 AN: 4824

European-Finnish (FIN) AF: 0.645 AC: 6823 AN: 10580

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

European-Non Finnish (NFE) AF: 0.661 AC: 44918 AN: 67986

Other (OTH) AF: 0.688 AC: 1454 AN: 2114

Alfa AF: 0.672 Hom.: 53541

Bravo AF: 0.670

Asia WGS AF: 0.690 AC: 2400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		0.25
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: rs4514547; hg19: chr13-40238899;