Genetic Variant COPG1:p.Ser134Ile (chr3-129254986-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016128.4(COPG1):c.401G>T(p.Ser134Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000124 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

COPG1
NM_016128.4 missense, splice_region

Scores

Splicing: ADA: 0.8188

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37817475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPG1	NM_016128.4 link	c.401G>T	p.Ser134Ile	missense_variant, splice_region_variant	Exon 7 of 24	ENST00000314797.10	NP_057212.1	Q9Y678

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPG1	ENST00000314797.10 link	c.401G>T	p.Ser134Ile	missense_variant, splice_region_variant	Exon 7 of 24	1	NM_016128.4	ENSP00000325002.6		Q9Y678

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.401G>T (p.S134I) alteration is located in exon 7 (coding exon 7) of the COPG1 gene. This alteration results from a G to T substitution at nucleotide position 401, causing the serine (S) at amino acid position 134 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.018

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.099

Sift

Uncertain

0.0090

Sift4G

Benign

0.077

Polyphen

0.50

Vest4

0.58

MutPred

0.55

Loss of MoRF binding (P = 0.2583);

MVP

0.24

MPC

0.45

ClinPred

0.95

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.82

dbscSNV1_RF

Pathogenic

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over