rs1491507046

Variant names:

• chr13-39724500-TTA-T
• rs1491507046
• NM_020751.3:c.1693-7_1693-6delTA

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_1693-6delTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 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, 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 rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.1693-7_1693-6delTA		splice_region_variant, intron_variant	Intron 16 of 18	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.1693-7_1693-6delTA		splice_region_variant, intron_variant	Intron 16 of 18		NP_001138551.1
COG6	XM_011535168.2	c.1693-7_1693-6delTA		splice_region_variant, intron_variant	Intron 16 of 19		XP_011533470.1
COG6	NR_026745.1	n.1858-7_1858-6delTA		splice_region_variant, intron_variant	Intron 17 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.1693-7_1693-6delTA		splice_region_variant, intron_variant	Intron 16 of 18	1	NM_020751.3	ENSP00000397441.2
COG6	ENST00000416691.5	c.1693-7_1693-6delTA		splice_region_variant, intron_variant	Intron 16 of 18	1		ENSP00000403733.1
COG6	ENST00000356576.8	n.*1530-7_*1530-6delTA		splice_region_variant, intron_variant	Intron 17 of 19	1		ENSP00000348983.4

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

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Congenital disorder of glycosylation Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Nov 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;