chr13-45465160-T-C

Position:

• chr13-45465160-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_031431.4(COG3):​c.124T>C​(p.Ser42Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COG3 NM_031431.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.73

Genes affected

COG3 (HGNC:18619): (component of oligomeric golgi complex 3) This gene encodes a component of the conserved oligomeric Golgi (COG) complex which is composed of eight different subunits and is required for normal Golgi morphology and localization. Defects in the COG complex result in multiple deficiencies in protein glycosylation. The protein encoded by this gene is involved in ER-Golgi transport.[provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755
• PP5: Variant 13-45465160-T-C is Pathogenic according to our data. Variant chr13-45465160-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 2584759.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG3	NM_031431.4	c.124T>C	p.Ser42Pro	missense_variant	1/23	ENST00000349995.10
COG3	XM_047430702.1	c.124T>C	p.Ser42Pro	missense_variant	1/19
COG3	XR_007063702.1	n.222T>C		non_coding_transcript_exon_variant	1/14
COG3	XR_429222.5	n.222T>C		non_coding_transcript_exon_variant	1/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG3	ENST00000349995.10	c.124T>C	p.Ser42Pro	missense_variant	1/23	1	NM_031431.4	P1
COG3	ENST00000617493.1	c.124T>C	p.Ser42Pro	missense_variant	1/12	1
COG3	ENST00000476702.1	c.97T>C	p.Ser33Pro	missense_variant	1/2	3
COG3	ENST00000617325.1	n.263T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital disorder of glycosylation, type IIbb Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.76	T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	N;.
REVEL	Benign	0.26
Sift	Benign	0.15	T;.
Sift4G	Benign	0.21	T;D
Polyphen		1.0	D;D
Vest4		0.70
MutPred		0.27		Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);
MVP		0.84
MPC		0.93
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.85
gMVP		0.88

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: chr13-46039295;