rs1555497604

Variant names:

• chr16-23452993-A-G
• rs1555497604
• NM_153603.4:c.2T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_153603.4(COG7):​c.2T>C​(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COG7 NM_153603.4 start_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.26
• Publications: 0 publications found

Genes affected

COG7 (HGNC:18622): (component of oligomeric golgi complex 7) The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010]

COG7 Gene-Disease associations (from GenCC):

• COG7-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics

ENSG00000260136 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 3 pathogenic variants. Next in-frame start position is after 42 codons. Genomic position: 23452871. Lost 0.054 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-23452993-A-G is Pathogenic according to our data. Variant chr16-23452993-A-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 548709.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153603.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG7	NM_153603.4	MANE Select	c.2T>C	p.Met1?	start_lost	Exon 1 of 17	NP_705831.1	A0A0S2Z652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG7	ENST00000307149.10	TSL:1 MANE Select	c.2T>C	p.Met1?	start_lost	Exon 1 of 17	ENSP00000305442.5	P83436
	COG7	ENST00000941095.1		c.2T>C	p.Met1?	start_lost	Exon 1 of 18	ENSP00000611154.1
	COG7	ENST00000916651.1		c.2T>C	p.Met1?	start_lost	Exon 1 of 17	ENSP00000586710.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	COG7 congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-0.31	T
PhyloP100		8.3
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.77		Loss of stability (P = 0.0013)
MVP		0.66
ClinPred		1.0	D
GERP RS		4.5
PromoterAI		-0.30	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.68
Mutation Taster		=6/194	disease causing (ClinVar)

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: rs1555497604; hg19: chr16-23464314; COSMIC: COSV100207325; COSMIC: COSV100207325;