chr13-45465167-T-C

Variant names:

• chr13-45465167-T-C
• NM_031431.4:c.131T>C

Variant summary

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

The NM_031431.4(COG3):​c.131T>C​(p.Leu44Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 3.99
• Publications: 0 publications found

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]

COG3 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type IIbb

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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=0.23410293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG3	NM_031431.4	c.131T>C	p.Leu44Ser	missense_variant	Exon 1 of 23	ENST00000349995.10	NP_113619.3
COG3	XM_047430702.1	c.131T>C	p.Leu44Ser	missense_variant	Exon 1 of 19		XP_047286658.1
COG3	XR_007063702.1	n.229T>C		non_coding_transcript_exon_variant	Exon 1 of 14
COG3	XR_429222.5	n.229T>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.131T>C	p.Leu44Ser	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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.131T>C (p.L44S) alteration is located in exon 1 (coding exon 1) of the COG3 gene. This alteration results from a T to C substitution at nucleotide position 131, causing the leucine (L) at amino acid position 44 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Benign	0.82
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	0.095
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	L;L
PhyloP100		4.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.11
Sift	Benign	0.81	T;.
Sift4G	Benign	0.40	T;D
Polyphen		0.29	B;B
Vest4		0.48
MutPred		0.26		Gain of phosphorylation at L44 (P = 0.042);Gain of phosphorylation at L44 (P = 0.042);
MVP		0.57
MPC		0.50
ClinPred		0.66	D
GERP RS		4.8
PromoterAI		0.0087	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.55
Mutation Taster		=66/34	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

hg19: chr13-46039302;