3-129252885-CGT-AGC

Variant names:

• chr3-129252885-CGT-AGC
• NM_016128.4:c.253_255delCGTinsAGC
• COPG1 p.Arg85Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_016128.4(COPG1):​c.253_255delCGTinsAGC​(p.Arg85Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R85C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COPG1 NM_016128.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.61
• Publications: 0 publications found

Genes affected

COPG1 (HGNC:2236): (COPI coat complex subunit gamma 1) Predicted to enable structural molecule activity. Predicted to be involved in several processes, including Golgi vesicle transport; establishment of Golgi localization; and organelle transport along microtubule. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

COPG1 Gene-Disease associations (from GenCC):

• non-severe combined immunodeficiency due to COPG1 deficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016128.4. 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
	COPG1	NM_016128.4	MANE Select	c.253_255delCGTinsAGC	p.Arg85Ser	missense	N/A	NP_057212.1	Q9Y678

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPG1	ENST00000314797.10	TSL:1 MANE Select	c.253_255delCGTinsAGC	p.Arg85Ser	missense	N/A	ENSP00000325002.6	Q9Y678
	COPG1	ENST00000961557.1		c.253_255delCGTinsAGC	p.Arg85Ser	missense	N/A	ENSP00000631616.1
	COPG1	ENST00000865885.1		c.253_255delCGTinsAGC	p.Arg85Ser	missense	N/A	ENSP00000535944.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-128971728;