rs3014960

chr13-45503246-G-Achr13-45503246-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_031431.4(COG3):c.1491G>A(p.Gln497=) 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. 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
COG3	NM_031431.4	c.1491G>A	p.Gln497=	splice_region_variant, synonymous_variant	14/23	ENST00000349995.10
COG3	XM_047430702.1	c.1491G>A	p.Gln497=	splice_region_variant, synonymous_variant	14/19
COG3	XR_007063702.1	n.1428G>A		splice_region_variant, non_coding_transcript_exon_variant	13/14
COG3	XR_429222.5	n.1589G>A		splice_region_variant, non_coding_transcript_exon_variant	14/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG3	ENST00000349995.10	c.1491G>A	p.Gln497=	splice_region_variant, synonymous_variant	14/23	1	NM_031431.4	P1
COG3	ENST00000465942.1	n.466G>A		splice_region_variant, non_coding_transcript_exon_variant	5/7	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

GnomAD3 exomes AF: 0.893 AC: 224020 AN: 250776 Hom.: 100159 AF XY: 0.892 AC XY: 120843 AN XY: 135540

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 SAS exome AF: 0.917

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

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.946

Gnomad4 ASJ exome AF: 0.909

Gnomad4 EAS exome AF: 0.903

Gnomad4 SAS exome AF: 0.914

Gnomad4 FIN exome AF: 0.835

Gnomad4 NFE exome AF: 0.882

Gnomad4 OTH exome AF: 0.891

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

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.921

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.882

Gnomad4 OTH AF: 0.903

Alfa AF: 0.889 Hom.: 100239

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3014960; hg19: chr13-46077381; COSMIC: COSV63072697;