chr7-107362380-A-C

Variant names:

• chr7-107362380-A-C
• rs74522314
• NM_006348.5:c.876T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006348.5(COG5):​c.876T>G​(p.Thr292Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,613,910 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (15 hom.)
• Consequence: COG5 NM_006348.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0350
• Publications: 2 publications found

Genes affected

COG5 (HGNC:14857): (component of oligomeric golgi complex 5) 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. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]

COG5 Gene-Disease associations (from GenCC):

• COG5-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 7-107362380-A-C is Benign according to our data. Variant chr7-107362380-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 358465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.035 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00849 (1293/152300) while in subpopulation AFR AF = 0.0284 (1179/41554). AF 95% confidence interval is 0.027. There are 23 homozygotes in GnomAd4. There are 630 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006348.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	NM_006348.5	MANE Select	c.876T>G	p.Thr292Thr	synonymous	Exon 9 of 22	NP_006339.4
	COG5	NM_181733.4		c.876T>G	p.Thr292Thr	synonymous	Exon 9 of 21	NP_859422.3
	COG5	NM_001161520.2		c.876T>G	p.Thr292Thr	synonymous	Exon 9 of 21	NP_001154992.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	ENST00000297135.9	TSL:1 MANE Select	c.876T>G	p.Thr292Thr	synonymous	Exon 9 of 22	ENSP00000297135.4
	COG5	ENST00000347053.8	TSL:1	c.876T>G	p.Thr292Thr	synonymous	Exon 9 of 21	ENSP00000334703.3
	COG5	ENST00000393603.7	TSL:1	c.876T>G	p.Thr292Thr	synonymous	Exon 9 of 21	ENSP00000377228.3

Frequencies

GnomAD3 genomes AF: 0.00848 AC: 1290 AN: 152182 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

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: 0.000397

Gnomad OTH AF: 0.00767

GnomAD2 exomes AF: 0.00235 AC: 592 AN: 251444 AF XY: 0.00181

Gnomad AFR exome AF: 0.0297

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00103 AC: 1509 AN: 1461610 Hom.: 15 Cov.: 33 AF XY: 0.000909 AC XY: 661 AN XY: 727128

African (AFR) AF: 0.0289 AC: 965 AN: 33438

American (AMR) AF: 0.00239 AC: 107 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000228 AC: 253 AN: 1111814

Other (OTH) AF: 0.00272 AC: 164 AN: 60382

GnomAD4 genome AF: 0.00849 AC: 1293 AN: 152300 Hom.: 23 Cov.: 32 AF XY: 0.00846 AC XY: 630 AN XY: 74480

African (AFR) AF: 0.0284 AC: 1179 AN: 41554

American (AMR) AF: 0.00451 AC: 69 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68026

Other (OTH) AF: 0.00759 AC: 16 AN: 2108

Alfa AF: 0.00583 Hom.: 5

Bravo AF: 0.00986

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	COG5-congenital disorder of glycosylation (2)
-	-	1	COG5-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.0
DANN	Benign	0.61
PhyloP100		0.035
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs74522314; hg19: chr7-107002825;