17-73193222-G-T

Variant names:

• chr17-73193222-G-T
• NM_018714.3:c.153G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018714.3(COG1):​c.153G>T​(p.Met51Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,740 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: COG1 NM_018714.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.67

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]

ENSG00000264860 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG1	NM_018714.3	c.153G>T	p.Met51Ile	missense_variant	Exon 1 of 14	ENST00000299886.9	NP_061184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG1	ENST00000299886.9	c.153G>T	p.Met51Ile	missense_variant	Exon 1 of 14	1	NM_018714.3	ENSP00000299886.4
COG1	ENST00000438720.7	c.150G>T	p.Met50Ile	missense_variant	Exon 1 of 13	1		ENSP00000400111.3
COG1	ENST00000582587.2	n.129G>T		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000462101.1
ENSG00000264860	ENST00000580671.1	n.502-3285G>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456740 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 724190

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	32
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Pathogenic	0.49	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.1	.;M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.5	.;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.87	.;P
Vest4		0.64
MutPred		0.59		Loss of disorder (P = 0.0721);Loss of disorder (P = 0.0721);
MVP		0.43
MPC		1.8
ClinPred		0.99	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-71189361; COSMIC: COSV55428337;