rs139304974

chr17-73197258-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018714.3(COG1):c.775G>T(p.Val259Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000715 in 1,614,224 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (3 hom.)
• Consequence: COG1 NM_018714.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.27

Genes affected

COG1 (HGNC:6545): (component of oligomeric golgi complex 1) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. It is thought that this protein is required for steps in the normal medial and trans Golgi-associated processing of glycoconjugates and plays a role in the organization of the Golgi-localized complex. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008938342).
• BP6: Variant 17-73197258-G-T is Benign according to our data. Variant chr17-73197258-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 235502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-73197258-G-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00389 (592/152330) while in subpopulation AFR AF= 0.0137 (569/41572). AF 95% confidence interval is 0.0128. There are 3 homozygotes in gnomad4. There are 268 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG1	NM_018714.3	c.775G>T	p.Val259Leu	missense_variant	4/14	ENST00000299886.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG1	ENST00000299886.9	c.775G>T	p.Val259Leu	missense_variant	4/14	1	NM_018714.3	P1
COG1	ENST00000438720.7	c.775G>T	p.Val259Leu	missense_variant	4/13	1

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 595 AN: 152212 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000942 AC: 237 AN: 251492 Hom.: 2 AF XY: 0.000662 AC XY: 90 AN XY: 135918

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000384 AC: 562 AN: 1461894 Hom.: 3 Cov.: 35 AF XY: 0.000311 AC XY: 226 AN XY: 727248

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.000380

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.000712

GnomAD4 genome AF: 0.00389 AC: 592 AN: 152330 Hom.: 3 Cov.: 33 AF XY: 0.00360 AC XY: 268 AN XY: 74494

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000803 Hom.: 10

Bravo AF: 0.00411

ESP6500AA AF: 0.0148 AC: 65

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00120 AC: 146

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

COG1 congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 04, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	23
Dann	Benign	0.97
DEOGEN2	Benign	0.0039	T;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;D
MetaRNN	Benign	0.0089	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.52	T;T
Polyphen		0.13	.;B
Vest4		0.37
MutPred		0.42		Loss of glycosylation at T264 (P = 0.5412);Loss of glycosylation at T264 (P = 0.5412);
MVP		0.35
MPC		0.22
ClinPred		0.036	T
GERP RS		5.8
Varity_R		0.095

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: rs139304974; hg19: chr17-71193397;