NM_015386.3:c.2356A>G

Variant names:

• chr16-70481024-T-C
• NM_015386.3:c.2356A>G

Variant summary

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

The NM_015386.3(COG4):​c.2356A>G​(p.Arg786Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COG4 NM_015386.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.649

Genes affected

COG4 (HGNC:18620): (component of oligomeric golgi complex 4) The protein encoded by this gene is a component of an oligomeric protein complex involved in the structure and function of the Golgi apparatus. Defects in this gene may be a cause of congenital disorder of glycosylation type IIj. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG4	NM_015386.3	c.2356A>G	p.Arg786Gly	missense_variant	Exon 19 of 19	ENST00000323786.10	NP_056201.2
COG4	NM_001195139.2	c.2281A>G	p.Arg761Gly	missense_variant	Exon 18 of 18		NP_001182068.2
COG4	NM_001365426.1	c.1930A>G	p.Arg644Gly	missense_variant	Exon 20 of 20		NP_001352355.1
COG4	NR_158212.1	n.2315A>G		non_coding_transcript_exon_variant	Exon 19 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG4	ENST00000323786.10	c.2356A>G	p.Arg786Gly	missense_variant	Exon 19 of 19	1	NM_015386.3	ENSP00000315775.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Apr 30, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.36	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.0	D;.;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.029	D;D;D
Vest4		0.83
MVP		0.46
MPC		0.70
ClinPred		0.97	D
GERP RS		2.3
gMVP		0.73

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: chr16-70514927;