3-39098460-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031899.4(GORASP1):​c.1099G>A​(p.Glu367Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,998 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: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

GORASP1
NM_031899.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24
Variant links:
Genes affected
GORASP1 (HGNC:16769): (golgi reassembly stacking protein 1) The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a membrane protein involved in establishing the stacked structure of the Golgi apparatus. It is a caspase-3 substrate, and cleavage of this encoded protein contributes to Golgi fragmentation in apoptosis. This encoded protein can form a complex with the Golgi matrix protein GOLGA2, and this complex binds to the vesicle docking protein p115. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15208322).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GORASP1NM_031899.4 linkc.1099G>A p.Glu367Lys missense_variant Exon 9 of 9 ENST00000319283.8 NP_114105.1 Q9BQQ3-1B3KPY8A0A024R2U5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GORASP1ENST00000319283.8 linkc.1099G>A p.Glu367Lys missense_variant Exon 9 of 9 1 NM_031899.4 ENSP00000313869.3 Q9BQQ3-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152188
Hom.:
0
Cov.:
33
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:
0.00116
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248496
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134576
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000901
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461810
Hom.:
0
Cov.:
31
AF XY:
0.0000179
AC XY:
13
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000298
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1099G>A (p.E367K) alteration is located in exon 9 (coding exon 9) of the GORASP1 gene. This alteration results from a G to A substitution at nucleotide position 1099, causing the glutamic acid (E) at amino acid position 367 to be replaced by a lysine (K). 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
0.26
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.24
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.0074
T;T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.0
M;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.79
N;N;N
REVEL
Benign
0.19
Sift
Uncertain
0.0090
D;D;D
Sift4G
Benign
0.55
T;T;T
Polyphen
0.99
D;D;D
Vest4
0.39
MutPred
0.37
Gain of ubiquitination at E367 (P = 0.0077);.;.;
MVP
0.26
MPC
0.57
ClinPred
0.48
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs745816319; hg19: chr3-39139951; API