chr7-107210554-A-T

Variant names:

• chr7-107210554-A-T
• rs773449359
• NM_006348.5:c.2347T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006348.5(COG5):​c.2347T>A​(p.Ser783Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S783P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COG5 NM_006348.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• Publications: 1 publications found

Genes affected

COG5 (HGNC:14857): (component of oligomeric golgi complex 5) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]

COG5 Gene-Disease associations (from GenCC):

• COG5-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16003057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG5	NM_006348.5	c.2347T>A	p.Ser783Thr	missense_variant	Exon 21 of 22	ENST00000297135.9	NP_006339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG5	ENST00000297135.9	c.2347T>A	p.Ser783Thr	missense_variant	Exon 21 of 22	1	NM_006348.5	ENSP00000297135.4
COG5	ENST00000347053.8	c.2284T>A	p.Ser762Thr	missense_variant	Exon 20 of 21	1		ENSP00000334703.3
COG5	ENST00000393603.7	c.2347T>A	p.Ser783Thr	missense_variant	Exon 21 of 21	1		ENSP00000377228.3
COG5	ENST00000464542.5	n.798T>A		non_coding_transcript_exon_variant	Exon 6 of 6	3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 233880 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451268 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720518

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 43326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.00 AC: 0 AN: 83766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107246

Other (OTH) AF: 0.00 AC: 0 AN: 60020

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;.
PhyloP100		4.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.31	T;T;T
Polyphen		0.0090	B;B;.
Vest4		0.45
MutPred		0.20		Gain of phosphorylation at S793 (P = 0.0362);.;.;
MVP		0.40
MPC		0.054
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.37
gMVP		0.37
Mutation Taster		=85/15	polymorphism

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: rs773449359; hg19: chr7-106850999;