rs1491507046

chr13-39724500-TTA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020751.3(COG6):c.1693-7_1693-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,227,282 control chromosomes in the GnomAD database, including 398 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 0)
  • Exomes 𝑓: 0.079 (396 hom.)
• Consequence: COG6 NM_020751.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.232

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 13-39724500-TTA-T is Benign according to our data. Variant chr13-39724500-TTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 312147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-39724500-TTA-T is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG6	NM_020751.3	c.1693-7_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000455146.8
COG6	NM_001145079.2	c.1693-7_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
COG6	XM_011535168.2	c.1693-7_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
COG6	NR_026745.1	n.1858-7_1858-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG6	ENST00000455146.8	c.1693-7_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020751.3	P1
COG6	ENST00000416691.5	c.1693-7_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
COG6	ENST00000356576.8	c.*1530-7_*1530-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00296 AC: 382 AN: 129132 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000955

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00658

Gnomad ASJ AF: 0.00208

Gnomad EAS AF: 0.000958

Gnomad SAS AF: 0.00935

Gnomad FIN AF: 0.00298

Gnomad MID AF: 0.0182

Gnomad NFE AF: 0.00314

Gnomad OTH AF: 0.00778

GnomAD4 exome AF: 0.0793 AC: 87062 AN: 1098064 Hom.: 396 AF XY: 0.0813 AC XY: 44296 AN XY: 545116

Gnomad4 AFR exome AF: 0.0745

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0567

Gnomad4 NFE exome AF: 0.0706

Gnomad4 OTH exome AF: 0.0882

GnomAD4 genome AF: 0.00296 AC: 382 AN: 129218 Hom.: 2 Cov.: 0 AF XY: 0.00307 AC XY: 192 AN XY: 62552

Gnomad4 AFR AF: 0.000953

Gnomad4 AMR AF: 0.00666

Gnomad4 ASJ AF: 0.00208

Gnomad4 EAS AF: 0.000960

Gnomad4 SAS AF: 0.00935

Gnomad4 FIN AF: 0.00298

Gnomad4 NFE AF: 0.00314

Gnomad4 OTH AF: 0.00773

Alfa AF: 0.00166 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

COG6-ongenital disorder of glycosylation;C3809160:Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1491507046; hg19: chr13-40298637; COSMIC: COSV62995331;