3-129249723-T-C

Variant names:

• chr3-129249723-T-C
• NM_016128.4:c.14T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016128.4(COPG1):​c.14T>C​(p.Phe5Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: COPG1 NM_016128.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.86
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35668314).

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.14T>C	p.Phe5Ser	missense	Exon 1 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.14T>C	p.Phe5Ser	missense	Exon 1 of 24	ENSP00000325002.6	Q9Y678
	COPG1	ENST00000961557.1		c.14T>C	p.Phe5Ser	missense	Exon 1 of 25	ENSP00000631616.1
	COPG1	ENST00000865885.1		c.14T>C	p.Phe5Ser	missense	Exon 1 of 25	ENSP00000535944.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399214 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690100

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078914

Other (OTH) AF: 0.00 AC: 0 AN: 57988

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Benign	0.93
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.090	N
REVEL	Benign	0.15
Sift	Benign	0.53	T
Sift4G	Benign	0.32	T
Polyphen		0.97	D
Vest4		0.51
MutPred		0.38		Loss of stability (P = 0.0047)
MVP		0.44
MPC		0.65
ClinPred		0.95	D
GERP RS		4.8
PromoterAI		0.090	Neutral
Varity_R		0.40
gMVP		0.28
Mutation Taster		=72/28	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

hg19: chr3-128968566;