Genetic Variant COG6:c.-43C>T (chr13-39655684-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_020751.3(COG6):c.-43C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,555,048 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000069 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000029 ( 1 hom. )

Consequence

COG6
NM_020751.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0840

Publications

0 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

COG6-congenital disorder of glycosylation
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COG6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 13-39655684-C-T is Benign according to our data. Variant chr13-39655684-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 669176.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3 link	c.-43C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1	Q9Y2V7-1A0A024RDW5
COG6	NM_020751.3 link	c.-43C>T		5_prime_UTR_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1	Q9Y2V7-1A0A024RDW5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8 link	c.-43C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2		Q9Y2V7-1
COG6	ENST00000455146.8 link	c.-43C>T		5_prime_UTR_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2		Q9Y2V7-1

Frequencies

GnomAD3 genomes

AF:

0.0000756

AC:

AN:

145550

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000219

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0100

Gnomad NFE

AF:

0.0000603

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000435

AC:

AN:

160992

AF XY:

0.0000576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000291

AC:

AN:

1409384

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

696442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31988

American (AMR)

AF:

0.000156

AC:

AN:

38466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25354

East Asian (EAS)

AF:

0.00

AC:

AN:

36454

South Asian (SAS)

AF:

0.00

AC:

AN:

80618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48806

Middle Eastern (MID)

AF:

0.000709

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.0000194

AC:

AN:

1083782

Other (OTH)

AF:

0.000172

AC:

AN:

58278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000687

AC:

AN:

145664

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

70896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39848

American (AMR)

AF:

0.000218

AC:

AN:

13730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

4828

South Asian (SAS)

AF:

0.00

AC:

AN:

4284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10156

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0000603

AC:

AN:

66300

Other (OTH)

AF:

0.00

AC:

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000604

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.8

(source)

DANN

Benign

0.88

PhyloP100

0.084

PromoterAI

0.013

Neutral

(source)

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

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13-39655684-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over