16-69339386-G-A

Position:

• chr16-69339386-G-A

Variant summary

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

The NM_032382.5(COG8):​c.167C>T​(p.Ser56Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COG8 NM_032382.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09

Genes affected

COG8 (HGNC:18623): (component of oligomeric golgi complex 8) This gene encodes a protein that is a component of the conserved oligomeric Golgi (COG) complex, a multiprotein complex that plays a structural role in the Golgi apparatus, and is involved in intracellular membrane trafficking and glycoprotein modification. Mutations in this gene cause congenital disorder of glycosylation, type IIh, a disease that is characterized by under-glycosylated serum proteins, and whose symptoms include severe psychomotor retardation, failure to thrive, seizures, and dairy and wheat product intolerance. [provided by RefSeq, Jul 2008]

ENSG00000260371 (HGNC:):

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=0.0947589).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG8	NM_032382.5	c.167C>T	p.Ser56Leu	missense_variant	1/6	ENST00000306875.10	NP_115758.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG8	ENST00000306875.10	c.167C>T	p.Ser56Leu	missense_variant	1/6	1	NM_032382.5	ENSP00000305459.6
ENSG00000260371	ENST00000563634.1	c.3-2674C>T		intron_variant		4		ENSP00000454500.1
ENSG00000259900	ENST00000564737.1	n.466-2674C>T		intron_variant		5		ENSP00000462747.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.167C>T (p.S56L) alteration is located in exon 1 (coding exon 1) of the COG8 gene. This alteration results from a C to T substitution at nucleotide position 167, causing the serine (S) at amino acid position 56 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0089	.;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.062
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.75	.;N;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.54	.;.;N
REVEL	Benign	0.11
Sift	Benign	0.54	.;.;T
Sift4G	Benign	0.43	.;.;T
Polyphen		0.028	B;B;.
Vest4		0.18
MutPred		0.47		.;Loss of phosphorylation at S56 (P = 0.0161);Loss of phosphorylation at S56 (P = 0.0161);
MVP		0.32
MPC		0.72
ClinPred		0.47	T
GERP RS		5.2
Varity_R		0.11
gMVP		0.23

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: chr16-69373289; COSMIC: COSV105039553; COSMIC: COSV105039553;