chr13-45523033-G-T

Variant names:

• chr13-45523033-G-T
• rs1536212
• NM_031431.4:c.2155-1943G>T

Variant summary

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

The NM_031431.4(COG3):​c.2155-1943G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,976 control chromosomes in the GnomAD database, including 8,724 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 0.32 (8724 hom., cov: 32)
• Consequence: COG3 NM_031431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG3	NM_031431.4	c.2155-1943G>T		intron_variant	Intron 19 of 22	ENST00000349995.10	NP_113619.3
COG3	XM_047430702.1	c.1931-1943G>T		intron_variant	Intron 17 of 18		XP_047286658.1
COG3	XR_429222.5	n.2253-1943G>T		intron_variant	Intron 19 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG3	ENST00000349995.10	c.2155-1943G>T		intron_variant	Intron 19 of 22	1	NM_031431.4	ENSP00000258654.8
COG3	ENST00000486940.2	n.116-1943G>T		intron_variant	Intron 1 of 5	2		ENSP00000477882.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48247 AN: 151856 Hom.: 8719 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.318 AC: 48274 AN: 151976 Hom.: 8724 Cov.: 32 AF XY: 0.321 AC XY: 23849 AN XY: 74240

African (AFR) AF: 0.146 AC: 6062 AN: 41456

American (AMR) AF: 0.422 AC: 6451 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3466

East Asian (EAS) AF: 0.266 AC: 1376 AN: 5178

South Asian (SAS) AF: 0.341 AC: 1646 AN: 4822

European-Finnish (FIN) AF: 0.410 AC: 4316 AN: 10514

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26365 AN: 67946

Other (OTH) AF: 0.308 AC: 647 AN: 2104

Alfa AF: 0.367 Hom.: 10618

Bravo AF: 0.310

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.79
PhyloP100		0.37
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: rs1536212; hg19: chr13-46097168;