13-39655752-T-A

Position:

• chr13-39655752-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020751.3(COG6):​c.26T>A​(p.Val9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.132

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11513299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG6	NM_020751.3	c.26T>A	p.Val9Asp	missense_variant	1/19	ENST00000455146.8
COG6	NM_001145079.2	c.26T>A	p.Val9Asp	missense_variant	1/19
COG6	XM_011535168.2	c.26T>A	p.Val9Asp	missense_variant	1/20
COG6	NR_026745.1	n.126T>A		non_coding_transcript_exon_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG6	ENST00000455146.8	c.26T>A	p.Val9Asp	missense_variant	1/19	1	NM_020751.3	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441078 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 715092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

COG6-ongenital disorder of glycosylation;C3809160:Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Feb 24, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with COG6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 9 of the COG6 protein (p.Val9Asp). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.97
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.33	N;N;.
REVEL	Benign	0.045
Sift	Benign	0.14	T;T;.
Sift4G	Benign	0.27	T;T;T
Polyphen		0.010	.;B;.
Vest4		0.48
MutPred		0.32		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.072
MPC		0.094
ClinPred		0.24	T
GERP RS		-4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-40229889;