13-39655660-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000416691.6(COG6):​c.-67A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,531,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

COG6
ENST00000416691.6 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.392

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COG6NR_026745.1 linkn.34A>G non_coding_transcript_exon_variant Exon 1 of 20
COG6NM_020751.3 linkc.-67A>G upstream_gene_variant ENST00000455146.8 NP_065802.1 Q9Y2V7-1A0A024RDW5
COG6NM_001145079.2 linkc.-67A>G upstream_gene_variant NP_001138551.1 Q9Y2V7-2A0A140VJG7
COG6XM_011535168.2 linkc.-67A>G upstream_gene_variant XP_011533470.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COG6ENST00000455146.8 linkc.-67A>G upstream_gene_variant 1 NM_020751.3 ENSP00000397441.2 Q9Y2V7-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152186
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000671
AC:
1
AN:
149126
AF XY:
0.0000125
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000890
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.25e-7
AC:
1
AN:
1379600
Hom.:
0
Cov.:
28
AF XY:
0.00000147
AC XY:
1
AN XY:
681842
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31264
American (AMR)
AF:
0.00
AC:
0
AN:
35914
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25060
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78854
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47126
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5652
European-Non Finnish (NFE)
AF:
9.41e-7
AC:
1
AN:
1062706
Other (OTH)
AF:
0.00
AC:
0
AN:
57328
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152304
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74480
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41578
American (AMR)
AF:
0.0000653
AC:
1
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000388
AC:
2
AN:
5156
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
5.9
DANN
Benign
0.66
PhyloP100
-0.39
PromoterAI
0.032
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs548475910; hg19: chr13-40229797; API