rs3014960

Variant names:

• chr13-45503246-G-A
• rs3014960
• NM_031431.4:c.1491G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-45503246-G-A
• chr13-45503246-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_031431.4(COG3):​c.1491G>A​(p.Gln497Gln) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.888 in 1,529,194 control chromosomes in the GnomAD database, including 604,205 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (61673 hom., cov: 32)
  • Exomes 𝑓: 0.89 (542532 hom.)
• Consequence: COG3 NM_031431.4 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.57
• Publications: 20 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG3	NM_031431.4	c.1491G>A	p.Gln497Gln	splice_region_variant, synonymous_variant	Exon 14 of 23	ENST00000349995.10	NP_113619.3
COG3	XM_047430702.1	c.1491G>A	p.Gln497Gln	splice_region_variant, synonymous_variant	Exon 14 of 19		XP_047286658.1
COG3	XR_007063702.1	n.1428G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 13 of 14
COG3	XR_429222.5	n.1589G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 14 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG3	ENST00000349995.10	c.1491G>A	p.Gln497Gln	splice_region_variant, synonymous_variant	Exon 14 of 23	1	NM_031431.4	ENSP00000258654.8
COG3	ENST00000465942.1	n.466G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 7	3

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136753 AN: 152112 Hom.: 61613 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.903

GnomAD2 exomes AF: 0.893 AC: 224020 AN: 250776 AF XY: 0.892

Gnomad AFR exome AF: 0.937

Gnomad AMR exome AF: 0.949

Gnomad ASJ exome AF: 0.907

Gnomad EAS exome AF: 0.874

Gnomad FIN exome AF: 0.837

Gnomad NFE exome AF: 0.876

Gnomad OTH exome AF: 0.892

GnomAD4 exome AF: 0.887 AC: 1221608 AN: 1376964 Hom.: 542532 Cov.: 21 AF XY: 0.888 AC XY: 612582 AN XY: 690056

African (AFR) AF: 0.940 AC: 29832 AN: 31734

American (AMR) AF: 0.946 AC: 42138 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 23235 AN: 25572

East Asian (EAS) AF: 0.903 AC: 35519 AN: 39322

South Asian (SAS) AF: 0.914 AC: 77102 AN: 84372

European-Finnish (FIN) AF: 0.835 AC: 44566 AN: 53342

Middle Eastern (MID) AF: 0.926 AC: 4902 AN: 5292

European-Non Finnish (NFE) AF: 0.882 AC: 913032 AN: 1035236

Other (OTH) AF: 0.891 AC: 51282 AN: 57532

GnomAD4 genome AF: 0.899 AC: 136872 AN: 152230 Hom.: 61673 Cov.: 32 AF XY: 0.899 AC XY: 66882 AN XY: 74414

African (AFR) AF: 0.938 AC: 38970 AN: 41538

American (AMR) AF: 0.921 AC: 14091 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3138 AN: 3472

East Asian (EAS) AF: 0.870 AC: 4508 AN: 5182

South Asian (SAS) AF: 0.912 AC: 4401 AN: 4826

European-Finnish (FIN) AF: 0.836 AC: 8829 AN: 10564

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 59968 AN: 68024

Other (OTH) AF: 0.903 AC: 1910 AN: 2116

Alfa AF: 0.891 Hom.: 121097

Bravo AF: 0.908

Asia WGS AF: 0.921 AC: 3199 AN: 3478

EpiCase AF: 0.885

EpiControl AF: 0.883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.7
DANN	Benign	0.93
PhyloP100		5.6
Mutation Taster		=97/3	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: rs3014960; hg19: chr13-46077381; COSMIC: COSV63072697;