13-45465160-T-C

Variant names:

• chr13-45465160-T-C
• rs1259403392
• NM_031431.4:c.124T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
COG3	NM_031431.4	c.124T>C	p.Ser42Pro	missense_variant	Exon 1 of 23	ENST00000349995.10	NP_113619.3
COG3	XM_047430702.1	c.124T>C	p.Ser42Pro	missense_variant	Exon 1 of 19		XP_047286658.1
COG3	XR_007063702.1	n.222T>C		non_coding_transcript_exon_variant	Exon 1 of 14
COG3	XR_429222.5	n.222T>C		non_coding_transcript_exon_variant	Exon 1 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG3	ENST00000349995.10	c.124T>C	p.Ser42Pro	missense_variant	Exon 1 of 23	1	NM_031431.4	ENSP00000258654.8

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

Oct 19, 2023

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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
PhyloP100		5.7
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
PromoterAI		0.016	Neutral
Varity_R		0.85
gMVP		0.88
Mutation Taster		=59/41	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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs1259403392; hg19: chr13-46039295;