13-39724501-TA-T

Position:

• chr13-39724501-TA-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.1693-4delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (11154 hom., cov: 0)
  • Exomes 𝑓: 0.25 (6667 hom.)
• Consequence: COG6 NM_020751.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.247

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 13-39724501-TA-T is Benign according to our data. Variant chr13-39724501-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 95991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG6	NM_020751.3	c.1693-4delA		splice_region_variant, intron_variant		ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.1693-4delA		splice_region_variant, intron_variant			NP_001138551.1
COG6	XM_011535168.2	c.1693-4delA		splice_region_variant, intron_variant			XP_011533470.1
COG6	NR_026745.1	n.1858-4delA		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.1693-4delA		splice_region_variant, intron_variant		1	NM_020751.3	ENSP00000397441.2
COG6	ENST00000416691.5	c.1693-4delA		splice_region_variant, intron_variant		1		ENSP00000403733.1
COG6	ENST00000356576.8	n.*1530-4delA		splice_region_variant, intron_variant		1		ENSP00000348983.4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 55616 AN: 131480 Hom.: 11153 Cov.: 0

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.518

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.249 AC: 268038 AN: 1075054 Hom.: 6667 Cov.: 16 AF XY: 0.250 AC XY: 133674 AN XY: 534660

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.423 AC: 55619 AN: 131516 Hom.: 11154 Cov.: 0 AF XY: 0.428 AC XY: 27178 AN XY: 63504

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.467

Alfa AF: 0.329 Hom.: 219

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 11, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 01, 2013	- -

Congenital disorder of glycosylation Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 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: rs66629036; hg19: chr13-40298638;