NM_020751.3:c.-41G>C

Variant names:

• chr13-39655686-G-C
• rs188328396
• NM_020751.3:c.-41G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020751.3(COG6):​c.-41G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,554,794 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000014 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000027 (1 hom.)
• Consequence: COG6 NM_020751.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.-41G>C		5_prime_UTR_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1
COG6	NR_026745.1	n.60G>C		non_coding_transcript_exon_variant	Exon 1 of 20
COG6	NM_001145079.2	c.-41G>C		5_prime_UTR_variant	Exon 1 of 19		NP_001138551.1
COG6	XM_011535168.2	c.-41G>C		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	c.-41G>C		5_prime_UTR_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.0000140 AC: 2 AN: 143014 Hom.: 0 Cov.: 34

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: 0.0000306

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000247 AC: 4 AN: 161758 AF XY: 0.0000343

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: 0.0000471

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000269 AC: 38 AN: 1411780 Hom.: 1 Cov.: 30 AF XY: 0.0000315 AC XY: 22 AN XY: 697882

African (AFR) AF: 0.00 AC: 0 AN: 32108

American (AMR) AF: 0.00 AC: 0 AN: 38926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 36626

South Asian (SAS) AF: 0.000173 AC: 14 AN: 80900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.0000221 AC: 24 AN: 1084960

Other (OTH) AF: 0.00 AC: 0 AN: 58328

GnomAD4 genome AF: 0.0000140 AC: 2 AN: 143014 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 69450

African (AFR) AF: 0.00 AC: 0 AN: 39202

American (AMR) AF: 0.00 AC: 0 AN: 13132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3324

East Asian (EAS) AF: 0.00 AC: 0 AN: 4728

South Asian (SAS) AF: 0.00 AC: 0 AN: 4144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000306 AC: 2 AN: 65438

Other (OTH) AF: 0.00 AC: 0 AN: 1916

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 03, 2017

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	-0.80
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		-2.1
PromoterAI		0.087	Neutral

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

Other links and lift over

dbSNP: rs188328396; hg19: chr13-40229823;