rs66629036

Variant names:

• chr13-39724501-TAA-T
• rs66629036
• NM_020751.3:c.1693-5_1693-4delAA

Your query was ambiguous. Multiple possible variants found:

• chr13-39724501-TAA-T
• chr13-39724501-TAA-TA
• chr13-39724501-TAA-TAAA
• chr13-39724501-TAA-TAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020751.3(COG6):​c.1693-5_1693-4delAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000891 in 1,122,048 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COG6 NM_020751.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 6 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	NM_020751.3	MANE Select	c.1693-5_1693-4delAA		splice_region intron	N/A	NP_065802.1	Q9Y2V7-1
	COG6	NM_001145079.2		c.1693-5_1693-4delAA		splice_region intron	N/A	NP_001138551.1	A0A140VJG7
	COG6	NR_026745.1		n.1858-5_1858-4delAA		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	ENST00000455146.8	TSL:1 MANE Select	c.1693-6_1693-5delAA		splice_region intron	N/A	ENSP00000397441.2	Q9Y2V7-1
	COG6	ENST00000416691.6	TSL:1	c.1693-6_1693-5delAA		splice_region intron	N/A	ENSP00000403733.1	Q9Y2V7-2
	COG6	ENST00000356576.8	TSL:1	n.*1530-6_*1530-5delAA		splice_region intron	N/A	ENSP00000348983.4	Q9Y2V7-4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 132000 Hom.: 0 Cov.: 0

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.91e-7 AC: 1 AN: 1122048 Hom.: 0 AF XY: 0.00000179 AC XY: 1 AN XY: 559930

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

African (AFR) AF: 0.00 AC: 0 AN: 25310

American (AMR) AF: 0.00 AC: 0 AN: 28966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19586

East Asian (EAS) AF: 0.00 AC: 0 AN: 30884

South Asian (SAS) AF: 0.0000163 AC: 1 AN: 61168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 863016

Other (OTH) AF: 0.00 AC: 0 AN: 46370

⚠️ 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 Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 132000 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 63718

African (AFR) AF: 0.00 AC: 0 AN: 35396

American (AMR) AF: 0.00 AC: 0 AN: 13376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3234

East Asian (EAS) AF: 0.00 AC: 0 AN: 4618

South Asian (SAS) AF: 0.00 AC: 0 AN: 4238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60898

Other (OTH) AF: 0.00 AC: 0 AN: 1836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

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: rs66629036; hg19: chr13-40298638;