NM_020751.3:c.624-3delT

Variant names:

• chr13-39679963-AT-A
• rs397756552
• NM_020751.3:c.624-3delT

Variant summary

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

The NM_020751.3(COG6):​c.624-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,390,130 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: COG6 NM_020751.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020751.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	NM_020751.3	MANE Select	c.624-3delT		splice_region intron	N/A	NP_065802.1
	COG6	NM_001145079.2		c.624-3delT		splice_region intron	N/A	NP_001138551.1
	COG6	NR_026745.1		n.789-3delT		splice_region intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	ENST00000455146.8	TSL:1 MANE Select	c.624-3delT		splice_region intron	N/A	ENSP00000397441.2
	COG6	ENST00000416691.6	TSL:1	c.624-3delT		splice_region intron	N/A	ENSP00000403733.1
	COG6	ENST00000356576.8	TSL:1	n.*461-3delT		splice_region intron	N/A	ENSP00000348983.4

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151474 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000100 AC: 23 AN: 230006 AF XY: 0.000112

Gnomad AFR exome AF: 0.0000695

Gnomad AMR exome AF: 0.000126

Gnomad ASJ exome AF: 0.000211

Gnomad EAS exome AF: 0.000179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000773

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000455 AC: 564 AN: 1238656 Hom.: 0 Cov.: 20 AF XY: 0.000436 AC XY: 273 AN XY: 626076

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000319 AC: 9 AN: 28236

American (AMR) AF: 0.0000690 AC: 3 AN: 43502

Ashkenazi Jewish (ASJ) AF: 0.000244 AC: 6 AN: 24546

East Asian (EAS) AF: 0.00 AC: 0 AN: 37734

South Asian (SAS) AF: 0.000217 AC: 17 AN: 78250

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52426

Middle Eastern (MID) AF: 0.000194 AC: 1 AN: 5164

European-Non Finnish (NFE) AF: 0.000554 AC: 508 AN: 916318

Other (OTH) AF: 0.000362 AC: 19 AN: 52480

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151474 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 73948

African (AFR) AF: 0.00 AC: 0 AN: 41250

American (AMR) AF: 0.00 AC: 0 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67810

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.43

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: rs397756552; hg19: chr13-40254100;