13-39679963-AT-ATT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_Moderate BP6_Very_Strong BA1

The NM_020751.3(COG6):​c.624-3dupT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,389,362 control chromosomes in the GnomAD database, including 35,440 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 0.27 (5858 hom., cov: 21)
  • Exomes 𝑓: 0.23 (29582 hom.)
• Consequence: COG6 NM_020751.3 splice_acceptor, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.428

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 -14 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.035967577 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.4, offset of 0 (no position change), new splice context is: atcattaattttttttttAGttt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BP6: Variant 13-39679963-A-AT is Benign according to our data. Variant chr13-39679963-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 198581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.624-3dupT		splice_acceptor_variant, intron_variant	Intron 6 of 18	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.624-3dupT		splice_acceptor_variant, intron_variant	Intron 6 of 18		NP_001138551.1
COG6	XM_011535168.2	c.624-3dupT		splice_acceptor_variant, intron_variant	Intron 6 of 19		XP_011533470.1
COG6	NR_026745.1	n.789-3dupT		splice_acceptor_variant, intron_variant	Intron 7 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.624-3dupT		splice_acceptor_variant, intron_variant	Intron 6 of 18	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41422 AN: 151418 Hom.: 5851 Cov.: 21

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.267

GnomAD3 exomes AF: 0.240 AC: 55295 AN: 230006 Hom.: 6292 AF XY: 0.242 AC XY: 30210 AN XY: 124968

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.289

Gnomad SAS exome AF: 0.242

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.231 AC: 285939 AN: 1237828 Hom.: 29582 Cov.: 20 AF XY: 0.232 AC XY: 144852 AN XY: 625694

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.274 AC: 41454 AN: 151534 Hom.: 5858 Cov.: 21 AF XY: 0.274 AC XY: 20261 AN XY: 74040

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.265

Bravo AF: 0.267

Asia WGS AF: 0.278 AC: 955 AN: 3432

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jun 12, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

not provided Benign:1

Jul 21, 2020

GeneDx

Significance: 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

Feb 03, 2025

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)		0.0		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: rs397756552; hg19: chr13-40254100;