Genetic Variant NM_020751.3:c.-21_-20insA (chr13-39655706-G-GA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020751.3(COG6):c.-21_-20insA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,486,116 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

COG6
NM_020751.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.32

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3 link	c.-21_-20insA	5_prime_UTR_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1	Q9Y2V7-1A0A024RDW5
COG6	NR_026745.1 link	n.80_81insA	non_coding_transcript_exon_variant	Exon 1 of 20
COG6	NM_001145079.2 link	c.-21_-20insA	5_prime_UTR_variant	Exon 1 of 19		NP_001138551.1	Q9Y2V7-2A0A140VJG7
COG6	XM_011535168.2 link	c.-21_-20insA	5_prime_UTR_variant	Exon 1 of 20		XP_011533470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8 link	c.-21_-20insA		5_prime_UTR_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2		Q9Y2V7-1

Frequencies

GnomAD3 genomes

AF:

0.0000363

AC:

AN:

55088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000775

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000335

AC:

AN:

59716

AF XY:

0.0000307

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000331

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000908

AC:

AN:

1431028

Hom.:

Cov.:

AF XY:

0.00000846

AC XY:

AN XY:

709170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32688

American (AMR)

AF:

0.00

AC:

AN:

41854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25588

East Asian (EAS)

AF:

0.0000264

AC:

AN:

37896

South Asian (SAS)

AF:

0.0000363

AC:

AN:

82694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.00000821

AC:

AN:

1095584

Other (OTH)

AF:

0.00

AC:

AN:

59002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000363

AC:

AN:

55088

Hom.:

Cov.:

AF XY:

0.0000754

AC XY:

AN XY:

26532

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17308

American (AMR)

AF:

0.00

AC:

AN:

2886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1052

East Asian (EAS)

AF:

0.00

AC:

AN:

1596

South Asian (SAS)

AF:

0.00

AC:

AN:

1158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000775

AC:

AN:

25796

Other (OTH)

AF:

0.00

AC:

AN:

650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-4.3

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

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NM_020751.3:c.-21_-20insA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over