rs755933277

Variant names:

• chr13-45465145-G-A
• rs755933277
• NM_031431.4:c.109G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-45465145-G-A
• chr13-45465145-G-C
• chr13-45465145-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_031431.4(COG3):​c.109G>A​(p.Asp37Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. D37H) has been classified as Pathogenic.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COG3 NM_031431.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.12
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr13-45465145-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 2584760.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.20634937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG3	NM_031431.4	c.109G>A	p.Asp37Asn	missense_variant	Exon 1 of 23	ENST00000349995.10	NP_113619.3
COG3	XM_047430702.1	c.109G>A	p.Asp37Asn	missense_variant	Exon 1 of 19		XP_047286658.1
COG3	XR_007063702.1	n.207G>A		non_coding_transcript_exon_variant	Exon 1 of 14
COG3	XR_429222.5	n.207G>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.109G>A	p.Asp37Asn	missense_variant	Exon 1 of 23	1	NM_031431.4	ENSP00000258654.8

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 244026 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000552

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461128 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726894

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		5.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.13
Sift	Benign	0.20	T;.
Sift4G	Benign	0.19	T;D
Polyphen		0.82	P;D
Vest4		0.17
MutPred		0.16		Loss of phosphorylation at S42 (P = 0.1806);Loss of phosphorylation at S42 (P = 0.1806);
MVP		0.70
MPC		0.33
ClinPred		0.94	D
GERP RS		4.8
PromoterAI		0.019	Neutral
Varity_R		0.26
gMVP		0.30
Mutation Taster		=86/14	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

dbSNP: rs755933277; hg19: chr13-46039280;