chr13-45465046-G-C

Position:

• chr13-45465046-G-C

Variant summary

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

The NM_031431.4(COG3):​c.10G>C​(p.Ala4Pro) 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. 13/21 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: COG3 NM_031431.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19765016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG3	NM_031431.4	c.10G>C	p.Ala4Pro	missense_variant	1/23	ENST00000349995.10
COG3	XM_047430702.1	c.10G>C	p.Ala4Pro	missense_variant	1/19
COG3	XR_007063702.1	n.108G>C		non_coding_transcript_exon_variant	1/14
COG3	XR_429222.5	n.108G>C		non_coding_transcript_exon_variant	1/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG3	ENST00000349995.10	c.10G>C	p.Ala4Pro	missense_variant	1/23	1	NM_031431.4	P1
COG3	ENST00000617493.1	c.10G>C	p.Ala4Pro	missense_variant	1/12	1
COG3	ENST00000617325.1	n.149G>C		non_coding_transcript_exon_variant	1/2	3
COG3	ENST00000476702.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.10G>C (p.A4P) alteration is located in exon 1 (coding exon 1) of the COG3 gene. This alteration results from a G to C substitution at nucleotide position 10, causing the alanine (A) at amino acid position 4 to be replaced by a proline (P). 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	0.20
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	0.96	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.72	N;.
REVEL	Benign	0.12
Sift	Uncertain	0.019	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.95	P;P
Vest4		0.28
MutPred		0.30		Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);
MVP		0.34
MPC		0.34
ClinPred		0.90	D
GERP RS		4.8
Varity_R		0.39
gMVP		0.66

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: chr13-46039181;