3-129254710-C-A

Variant names:

• chr3-129254710-C-A
• rs1256193425
• NM_016128.4:c.366C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_016128.4(COPG1):​c.366C>A​(p.Gly122Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G122G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COPG1 NM_016128.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.053 with no splicing effect.

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.366C>A	p.Gly122Gly	synonymous	Exon 6 of 24	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.366C>A	p.Gly122Gly	synonymous	Exon 6 of 24	ENSP00000325002.6	Q9Y678
	COPG1	ENST00000961557.1		c.366C>A	p.Gly122Gly	synonymous	Exon 6 of 25	ENSP00000631616.1
	COPG1	ENST00000865885.1		c.366C>A	p.Gly122Gly	synonymous	Exon 6 of 25	ENSP00000535944.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.2
DANN	Benign	0.70
PhyloP100		0.053
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs1256193425; hg19: chr3-128973553;