rs375280565

chr13-39724499-TTTA-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_020751.3(COG6):c.1693-8_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 0.00473 in 1,317,946 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0047 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: COG6 NM_020751.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -12 ACMG points.

• BP6: Variant 13-39724499-TTTA-T is Benign according to our data. Variant chr13-39724499-TTTA-T is described in ClinVar as [Benign]. Clinvar id is 540362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00473 (6231/1317946) while in subpopulation AMR AF= 0.0105 (386/36634). AF 95% confidence interval is 0.00967. There are 3 homozygotes in gnomad4_exome. There are 3113 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG6	NM_020751.3	c.1693-8_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000455146.8
COG6	NM_001145079.2	c.1693-8_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
COG6	XM_011535168.2	c.1693-8_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
COG6	NR_026745.1	n.1858-8_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.1693-8_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020751.3	P1
COG6	ENST00000416691.5	c.1693-8_1693-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
COG6	ENST00000356576.8	c.*1530-8_*1530-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 14 AN: 129554 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000640

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000663

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00473 AC: 6231 AN: 1317946 Hom.: 3 AF XY: 0.00474 AC XY: 3113 AN XY: 656884

Gnomad4 AFR exome AF: 0.00411

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00507

Gnomad4 EAS exome AF: 0.00531

Gnomad4 SAS exome AF: 0.00680

Gnomad4 FIN exome AF: 0.00294

Gnomad4 NFE exome AF: 0.00442

Gnomad4 OTH exome AF: 0.00477

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000108 AC: 14 AN: 129554 Hom.: 0 Cov.: 0 AF XY: 0.000127 AC XY: 8 AN XY: 62878

Gnomad4 AFR AF: 0.0000560

Gnomad4 AMR AF: 0.000640

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.0000663

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000169 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

COG6-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 30, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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 15, 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: rs375280565; hg19: chr13-40298636; COSMIC: COSV62997612;