NM_031431.4:c.124T>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The NM_031431.4(COG3):​c.124T>A​(p.Ser42Thr) 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. 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. S42P) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COG3 NM_031431.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: 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.
• BP4: Computational evidence support a benign effect (MetaRNN=0.35595888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG3	NM_031431.4	c.124T>A	p.Ser42Thr	missense_variant	Exon 1 of 23	ENST00000349995.10	NP_113619.3
COG3	XM_047430702.1	c.124T>A	p.Ser42Thr	missense_variant	Exon 1 of 19		XP_047286658.1
COG3	XR_007063702.1	n.222T>A		non_coding_transcript_exon_variant	Exon 1 of 14
COG3	XR_429222.5	n.222T>A		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>A	p.Ser42Thr	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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.74	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.9	L;L
PhyloP100		5.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.099
Sift	Benign	0.85	T;.
Sift4G	Benign	0.47	T;D
Polyphen		0.99	D;D
Vest4		0.39
MutPred		0.27		Gain of glycosylation at S42 (P = 0.0983);Gain of glycosylation at S42 (P = 0.0983);
MVP		0.72
MPC		0.54
ClinPred		0.92	D
GERP RS		4.8
PromoterAI		0.041	Neutral
Varity_R		0.46
gMVP		0.63
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1259403392; hg19: chr13-46039295;