rs3794331

Variant names:

• chr13-45479409-T-G
• rs3794331
• NM_031431.4:c.383+343T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031431.4(COG3):​c.383+343T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 152,196 control chromosomes in the GnomAD database, including 834 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.091 (834 hom., cov: 32)
• Consequence: COG3 NM_031431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG3	NM_031431.4	c.383+343T>G		intron_variant	Intron 3 of 22	ENST00000349995.10	NP_113619.3
COG3	XM_047430702.1	c.383+343T>G		intron_variant	Intron 3 of 18		XP_047286658.1
COG3	XR_007063702.1	n.481+343T>G		intron_variant	Intron 3 of 13
COG3	XR_429222.5	n.481+343T>G		intron_variant	Intron 3 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG3	ENST00000349995.10	c.383+343T>G		intron_variant	Intron 3 of 22	1	NM_031431.4	ENSP00000258654.8
COG3	ENST00000617493.1	c.383+343T>G		intron_variant	Intron 3 of 11	1		ENSP00000481332.1

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13885 AN: 152078 Hom.: 828 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0600

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0915 AC: 13924 AN: 152196 Hom.: 834 Cov.: 32 AF XY: 0.0912 AC XY: 6785 AN XY: 74428

African (AFR) AF: 0.158 AC: 6551 AN: 41522

American (AMR) AF: 0.0599 AC: 916 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3470

East Asian (EAS) AF: 0.110 AC: 566 AN: 5166

South Asian (SAS) AF: 0.0653 AC: 315 AN: 4824

European-Finnish (FIN) AF: 0.0828 AC: 876 AN: 10586

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0638 AC: 4336 AN: 68012

Other (OTH) AF: 0.0705 AC: 149 AN: 2114

Alfa AF: 0.0714 Hom.: 1849

Bravo AF: 0.0918

Asia WGS AF: 0.104 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.063
Mutation Taster		=100/0	polymorphism (auto)

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: rs3794331; hg19: chr13-46053544;