rs769454681
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_004287.5(GOSR2):āc.358A>Gā(p.Met120Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,502 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000041 ( 0 hom. )
Consequence
GOSR2
NM_004287.5 missense
NM_004287.5 missense
Scores
2
1
16
Clinical Significance
Conservation
PhyloP100: 9.28
Genes affected
GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a mutagenesis_site Loss of interaction with SEC24C. (size 0) in uniprot entity GOSR2_HUMAN
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GOSR2 | NM_004287.5 | c.358A>G | p.Met120Val | missense_variant | 5/6 | ENST00000640051.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GOSR2 | ENST00000640051.2 | c.358A>G | p.Met120Val | missense_variant | 5/6 | 1 | NM_004287.5 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251456Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
GnomAD3 exomes
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135896
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460502Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3AN XY: 726694
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces methionine with valine at codon 120 of the GOSR2 protein (p.Met120Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs769454681, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with GOSR2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;.;D;.;D;.;.;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;D;D;T;D;T;D;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;.;L;.;L;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
REVEL
Benign
Sift
Benign
.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G
Benign
.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Polyphen
0.11, 0.0050
.;B;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4
0.43
MutPred
Loss of disorder (P = 0.1376);Loss of disorder (P = 0.1376);.;.;Loss of disorder (P = 0.1376);Loss of disorder (P = 0.1376);Loss of disorder (P = 0.1376);.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP
0.60
MPC
0.18
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at